Therapeutic Treatment

ABSTRACT

This invention discloses a treatment for a patient receiving medication to treat an attention deficit disorder such as ADHD wherein the treatment results in a loss of appetite and impairment of the patient&#39;s attentiveness. The treatment combines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases the caloric intake of a patient, which can increase the patient&#39;s attentiveness. The combination treatment can be given for an indefinite, including, without limitation, life-long, to allow a patient to maintain normal caloric intake during treatment for an attention deficit disorder.

This application is a continuation of U.S. patent application Ser. No.14/046,528, filed on Oct. 4, 2013, which claims the benefit of priorityto U.S. Provisional Patent Application 61/744,948, filed on Oct. 4,2012, which is hereby incorporated by reference in its entirety.

BACKGROUND

To treat psychological and/or neurological disorders, including withoutlimitation, attention deficit disorder, migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression, neural insult, fatigue, lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, disease relatedfatigue in depression and fibromyalgia, cocaine addiction, Parkinson'sDisease, combat and non-combat related PTSD, tic, and any otherpsychological and/or neurological syndrome it is common to prescribe toa patient a therapeutic regimen that includes an amphetamine and/ormethylphenidate. An attention deficit disorder for which thesetherapeutics are generally prescribed is attention deficit hyperactivitydisorder, also known as ADHD. ADHD is one of the most common childhoodpsychiatric conditions. It has been diagnosed in approximately 8.4% ofall children aged 3-17 years old (Center for Disease Control andPrevention). Although scientists and clinicians debate the best way todiagnose and treat ADHD, there is no debate among competent andwell-informed health care professionals that ADHD is a validneurobiological condition that causes significant impairment to childrenwho suffer from it.

The clinical practice parameters followed by doctors inform them thatADHD is a chronic condition that will most likely to persist intoadulthood. The current standard of care recommendations state treatmentshould be 7 days a week, 12 months a year with no drug holidays. (see,for example, AACAP, 2007). Untreated ADHD is to known to havesignificant long-term consequences including loss of academicperformance, social performance, and more aberrant behaviors includingsubstance abuse, teen pregnancies and imprisonment.

Among the functional impacts of ADHD in children and adolescents are ahigher risk of injury, including, without limitation bicycle/pedestrianinjury, head injury and multiple injuries that require admission to anintensive care unit. Other functional impacts of ADHD include a higherrate of failure in school, higher risk of expulsion or dropout, higherrate of associated learning disability and lower rates of high school orcollege completion. Additionally, functional impacts of ADHD include alack of friendships, less liked by their peers compared to non-ADHDpeers, difficulty retaining peer status, a two times higher risk fortobacco smoking, a two and a half time higher risk for alcohol abuse, atwo times higher risk for substance abuse, are four times more likely tocontract an STD, a ten times higher risk for unplanned pregnancy, a twoto six times higher rate of suspended or revoked driver's license, moretraffic violations and speeding tickets, more motor vehicle accidentsand greater vehicular damage. (Goodman D W, Primary Psychiatry: 17, 22010)

Among the function impacts of ADHD in adults are similar to those foundin children and adolescents, but also include a higher likelihood ofbeing fired or quitting a job impulsively, reduced salary, poorer workperformance scores, more frequent job changes, three times more likelyto be unemployed, lower occupational attainment than patient IQ wouldpredict. Other functional impacts include a two times more likely chanceto be arrested, three times more likely to be convicted, fifteen timesmore likely to be incarcerated, a greater tendency towardantisocial/criminal behaviour, a lower household income, higher accidentclaims and higher cost of accidents. (Goodman D W, Primary Psychiatry:17, 2 2010)

Various drugs and methods have been used to treat ADHD, includingamphetamine and methylphenidate based drugs. While these drugs aregenerally effective in treating ADHD, the side effects suffered by thechildren taking them can include loss of appetite resulting in weightloss, insomnia, drug dependence and loss of attentiveness.

With regard to treatments for ADHD, one option generally followed byclinicians is to prescribe the use of short-acting stimulants. These areoften used as an initial treatment in small children (<16 kg), but thesedrugs have the disadvantage of requiring that they be administered twicea day (“b.i.d.”) or three times a day (“t.i.d.”) to provide control overa child's ADHD symptoms throughout day. Longer acting stimulants offergreater convenience, confidentiality, and compliance with single dailydosing, but the side effects suffered with these once a day drugs bychildren taking them is frequently more severe than the b.i.d. or t.i.d.ones.

But there are significant problems with therapeutic use of amphetaminesand methylphenidates for the treatment of any neurological orpsychological syndrome. For ADHD, the drugs are reported to beassociated with loss of appetite in roughly 35% of patients as well asweight loss in approximately 15% of patients. In practice, it is notunusual to find that the frequency of appetite reduction and the amountof weight loss is actually greater than what has been reported in thescientific literature. (Sears clinical observation). While this effectis perceived as positive by patients who are taking amphetamines as aweight loss medication, it can be detrimental to the health and properdevelopment of children taking medications for ADHD and otherpsychiatric disorders.

It is widely recognized in ADHD patients, and especially in children,that there is a documented link between patients missing meals andlearning impairment. For instance, overnight and morning fasting amongschoolchildren was found to have a deleterious effect on the children'smemory, attention, performance in academic pursuits and ability tointeract with other children socially. (Pollitt et al., 1998; Pollittand Gorman, 1994). This correlates with the finding that regularity inbreakfast consumption has been linked with improvement in academicperformance and psychosocial functioning as well as cognition amongchildren. (Benton, 2001; Bellisle, 2004).

It has been widely recognized that there is a documented link betweenmissing meals and learning impairment for ADHD patients as well aspatients suffering from a neurological or psychological syndrome. Apossible reason for this link may be a drop in glucose levels resultingfrom missing a meal, since the supply of glucose to the brain isbelieved to impact upon memory, mood and attentiveness. Researchsuggests that when engaging in cognitively demanding tasks, such asschoolwork, repeated supplies of glucose to the brain enhances cognitivefunctioning and improves memory, mood and attentiveness. Research on theimmediate effects of glucose on cognition demonstrated that the abilityof the brain to fully function appears to be sensitive to short-termfluctuations in glucose supply. (Bellisle, 2004). Patients withnutritional deficiencies are particularly susceptible to the short-termfluctuations in glucose supply that impact upon cognitive ability,attentiveness and performance of the brain. Maintaining adequate levelsof glucose throughout the day contributes to optimizing cognition andattentiveness, suggesting that nutritional intake should be designed tosustain an adequate level of glucose by minimizing fluctuations in foodintake during the day.

One way to overcome issues with appetite in patients with ADHD is forthe parents, spouse or other caregiver to actively monitor a patient'sfood intake. However, this generally only works when the patient is notresistant to eating, for instance, due to loss of appetite. Moreover,parents, spouse, or other caregiver cannot generally spend all day witha patient. This is particularly true when a majority of patients spendat least a portion of their day at school or work where they eat lunch.

Clinical guidelines for ADHD have tried to cope with appetite reductionand ADHD medication. (See for example, AACAP, 2007). Particularly, wherea patient suffers deleterious effects resulting from a loss of appetiteincluding slower growth in their height, a slowing in their weight gainand a loss in the child's attentiveness. The general standard is that ifa patient has a change in height or weight that crosses two percentilelines, then this suggests an aberrant growth trajectory. In these casesthe general response is for the child to stop taking the drug used totreat ADHD during weekends or during a patient's vacation or summerbreak if in school in order to attempt to mitigate the harm suffered bythe patient. One problem with this approach is that it can lead to themarked impairment of attentiveness by a patient during the periods oftime when their ADHD medication is removed. One option available to aclinician is to switch the patient to a different ADHD medication.However, as these drugs are also often either an amphetamine or amethylphenidate, it is likely that the patient will suffer from the sameside effects. Knowing both the benefits and side effects of currenttreatment regimens, in making a treatment decision, it is incumbent upona clinician to carefully balance the benefits of medication treatmentwith the risks of reductions in height and weight gain and the loss ofattentiveness resulting from a lack of appetite.

Therefore it would be preferable to treat the side effects such asappetite reduction that prevent the proper use and optimal levels ofamphetamine and/or methylphenidate therapy that are necessary to meetthe treatment guidelines to treat ADHD or other neurological orpsychological syndrome. One way to do this is through the use ofappetite stimulants. These include, but are not limited to, a diversegroup of medications given to patients to prevent undesired weight lossin the elderly and in patients suffering from such diseases as AIDS andcancer, diseases often associated with the wasting of the body's muscletissue as well as overall weight loss. The medical term for these drugsis orexigenic, which is derived from the Greek word for “appetite” or“desire” and includes various drugs, including, without limitation,hormones, vitamins or other compounds known to increase appetite. Thiscan include a naturally occurring neuropeptide hormone such as ghrelin,orexin or neuropeptide Y, or a drug or compound that increases hungerand therefore enhances food consumption.

An example of an appetite enhancement drug is cyproheptadinehydrochloride(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidinehydrochloride) (“cyproheptadine”). This drug has been used as oralmonotherapy for allergy under the tradename Periactin®. It is known toreach peak plasma levels in 1-3 hours after administration and has ahalf-life of 8 hours. (Gunja, 2004). In the 1960s, it was recognizedthat this drug had several side effects that made it a suboptimalallergy treatment. Among the side effects were weight gain anddrowsiness.

While weight gain was a side effect that made cyproheptadine a poorantihistamine, this side effect is desirable in children sufferingweight loss due to loss of appetite from use of amphetamines ormethylphenidates to treat ADHD. Cyproheptadine has been shown to causeweight gain in studies that used either non-human animals or humans.(Orthen-Gambill 1988). It has also been studied for its ability topromote weight gain in clinical trials for cancer cachexia. (Coulris).Other areas where there is interest in cyproheptadine to promote weightgain are tuberculosis, anorexia nervosa, cystic fibrosis, migraine,attention deficit disorder, migraine, anti-serotonergic side effects,underweight children, narcolepsy and any other psychological and/orneurological syndrome. (Coulris, Halm, Kardinal).

In ADHD, there is anecdotal evidence that a combination of anamphetamine or a methylphenidate and cyproheptadine as a treatment forchildren suffering from ADHD can result in weight gain and excessivesleep. (Daviss 2004). In the report, a number of children wereadministered their ADHD drug along with 4-8 mg of cyproheptadine atnight before they went to sleep. While this report suggests that theremay be a benefit of using cyproheptadine in ADHD children who aresuffering weight loss as a result of taking an amphetamine ormethylphenidate drug, it did not identify whether the resultant weightgain was due to the child eating over a regular eating cycle, forinstance, breakfast, lunch and/or dinner or due to eating over a shortperiod of time during which the cyproheptadine affects the child'sappetite, followed by hunger during the day after the effect of theeffects of the cyproheptadine have worn off. Nor did the report identifywhether the administration of cyproheptadine had an effect on a child'sattentiveness and ability to function cognitively and socially.Additionally, the report did not analyze the impact on height. Based onthe 8 hour half-life of cyproheptadine and its administration before bedin Daviss, it is not likely that children receiving the appetitestimulant had their appetites stimulated in a manner that would resultin their eating food during their waking hours. Thus, though it is notreported in Daviss, it is likely that while the children gained weight,they did not see a cyproheptadine-related improvement in attentivenessduring the day, particularly, while attending school.

It is an aim of the present invention to provide a pharmaceuticalcomposition wherein a patient suffering from a psychological and/orneurological disorder, including, without limitation, attention deficitdisorder (including, without limitation ADHD), migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and anyother psychological and/or neurological syndrome is provided anamphetamine and/or a methylphenidate drug and a drug that promotes anincrease in appetite. It is a further aim of the present invention toprovide a pharmaceutical composition wherein a patient suffering from apsychological and/or neurological disorder, including, withoutlimitation, attention deficit disorder (including, without limitationADHD), migraine, anti-serotonergic side effects, narcolepsy, excessivesleepiness associated with shift work, obstructive sleep apnea as anadjunct to continuous positive airways pressure (“CPAP”), exogenousobesity, disruptive behaviour disorder including oppositional defiantdisorder (“ODD”) and conduct disorder (“CD”), obesity, depression(including, without limitation, augmentation of antidepressants intreating refractory depression and cancer-related depression), neuralinsult, fatigue (including, without limitation, disease-related fatiguein patients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and anyother psychological and/or neurological syndrome is provided anamphetamine and/or methylphenidate drug and a drug that promotes anincrease in appetite, while maintaining or increasing the attentivenessby the patient when compared to a patient not receiving the appetitestimulant. It is an additional aim of the present invention to provide apharmaceutical composition wherein a patient suffering from apsychological and/or neurological disorder, including, withoutlimitation, attention deficit disorder (including, without limitationADHD), migraine, anti-serotonergic side effects, narcolepsy, excessivesleepiness associated with shift work, obstructive sleep apnea as anadjunct to continuous positive airways pressure (“CPAP”), exogenousobesity, disruptive behaviour disorder including oppositional defiantdisorder (“ODD”) and conduct disorder (“CD”), obesity, depression(including, without limitation, augmentation of antidepressants intreating refractory depression and cancer-related depression), neuralinsult, fatigue (including, without limitation, disease-related fatiguein patients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic and anyother psychological and/or neurological syndrome is provided anamphetamine and/or methylphenidate drug and a drug that promotes anincrease in appetite during the day that results in the maintenance oran increase in the attentiveness by the patient during the day whencompared to a patient not receiving the appetite stimulant. It is afurther aim of the present invention to provide a pharmaceuticalcomposition wherein a patient suffering from a psychological and/orneurological disorder, including, without limitation, attention deficitdisorder (including, without limitation ADHD), migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and anyother psychological and/or neurological syndrome is provided anamphetamine and/or methylphenidate drug and a drug that promotes anincrease in appetite during the day that results in the maintenance oran increase in the attentiveness by the patient during the day while atschool, work or other situation where the patient learns, works orinteracts with other people as compared to a patient not receiving theappetite stimulant. It is a further aim of the present invention toprovide a pharmaceutical composition wherein a patient suffering from apsychological and/or neurological disorder, including, withoutlimitation, attention deficit disorder (including, without limitationADHD), migraine, anti-serotonergic side effects, narcolepsy, excessivesleepiness associated with shift work, obstructive sleep apnea as anadjunct to continuous positive airways pressure (“CPAP”), exogenousobesity, disruptive behaviour disorder including oppositional defiantdisorder (“ODD”) and conduct disorder (“CD”), obesity, depression(including, without limitation, augmentation of antidepressants intreating refractory depression and cancer-related depression), neuralinsult, fatigue (including, without limitation, disease-related fatiguein patients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and anyother psychological and/or neurological syndrome is provided anamphetamine and/or methylphenidate drug and a drug that promotes anincrease in appetite during the day that results in an increase in theheight of the patient taking such medication versus the same patient ifsuch medication is not taken. By following such a therapeutic regimen, apatient will suffer fewer side effects resulting from appetite loss thatcan reduce treatment success and compliance, while maintaining areasonable degree of attentiveness during the day, including, withoutlimitation maintaining a reasonable degree of cognition and socialability.

SUMMARY OF THE INVENTION

Aspects of the present specification disclose a method of treating anindividual with a psychological and/or neurological disorder, including,without limitation, an attention deficit disorder, the method comprisesthe step of administering to an individual in need thereof apharmaceutical composition which comprises administration of atherapeutic compound to treat the attention deficit disorder and atherapeutic compound to treat a reduction in appetite. Aspects of thepresent specification further disclose a pharmaceutical compositioncomprising a therapeutic compound for a psychological and/orneurological disorder, including, without limitation, an attentiondeficit disorder and a therapeutic compound for a disorder associatedwith a reduction in appetite, wherein the pharmaceutical compositionreduces a symptom of a psychological and/or neurological disorder,including, without limitation, a disorder associated with an attentiondeficit disorder. Aspects of the present specification disclosetreatments that can result in an increase in attentiveness, weightand/or height of the individual, thereby treating the individual.

Aspects of the present specification disclose a treatment for aneurological and/or psychological disorder, including withoutlimitation, attention deficit disorder, and further without limitation,Attention Deficit Hyperactivity Disorder (ADHD) are treated in anindividual with an amphetamine or a methylphenidate.

Aspects of the present specification disclose, without limitation, thatan amphetamine or methylphenidate can be selected from the groupconsisting of OROS methylphenidate (Concerta), dextroamphetamineimmediate/sustained release (Adderall/Adderall XR), dexmethylphenidate(Focalin), Focalin XR, Metadate CD, Metadate ER, NWP09, Dexedrine,dextroamphetamine (Dexedrine), Dexedrine Spansules, Methylin ER (RitalinSR), methylphenidate (Ritalin), and methylphenidate CR, Ritalin, RitalinLA, SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin,Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch, Methylin chewable,Methylin liquid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTSpatch, Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa,Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil,Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, Remeron,Cymbalta, Nardil, Parnate, Emsam patch, Haldol, Orap, Prolixin,Mellaril, Thorazine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa,Seroquel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan,Buspar, Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid,Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, Topamax,Neurontin and the therapeutic compounds identified in Table 1.

Aspects of the present specification disclose that the symptomsassociated with attention deficit disorder is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95% and the severity associated with attentiondeficit disorder is reduced by at least 10%, at least 15%, at least 20%,at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, atleast 50%, at least 55%, at least 60%, at least 65%, at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, or at least 95%.Aspects of the present specification disclose the symptoms associatedwith attention deficit disorder is reduced by about about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%.

Aspects of the present specification disclose a dose of a therapeuticcompound to treat the disorder is in the range of at least 0.001mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/day, at least 15mg/kg/day, at least 20 mg/kg/day, at least 25 mg/kg/day, at least 30mg/kg/day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45mg/kg/day, or at least 50 mg/kg/day or in the range of about 0. 001mg/kg/day to about 100 mg/kg/day or in the range of about 0.001mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to about 15mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, about 0.001mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day to about 30mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100mg/kg/day.

Aspects of the present specification disclose, without limitation, atherapeutic compound to treat the disorder is administered to anindividual topical, sublingual, rectal, vaginal, trancutaneous, oral,inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.Aspects of the present specification disclose, without limitation atherapeutic compound to treat the attention deficit disorder isadministered as a liquid, a solid, a semi-solid or an aerosol and atherapeutic compound is formulated as a tablet, lozenge, orallydissolved strip, capsule, syrup, oral suspension, emulsion, granule,sprinkle or pellet.

Aspects of the present specification disclose, without limitation, atherapeutic compound is a long acting, sustained release, extendedrelease, immediate release, slow release, or controlled releasetherapeutic compound and the therapeutic compound is released over aperiod of about 3 days after administration, about 7 days afteradministration, about 10 days after administration, about 15 days afteradministration, about 20 days after administration, about 25 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration, or about 90 days after administration or is releasedover a period of at least 3 days after administration, at least 7 daysafter administration, at least 10 days after administration, at least 15days after administration, at least 20 days after administration, atleast 25 days after administration, at least 30 days afteradministration, at least 45 days after administration, at least 60 daysafter administration, at least 75 days after administration, or at least90 days after administration or is released over a period of about 1 dayafter administration, about 2 days after administration, about 3 daysafter administration, about 4 days after administration, about 5 daysafter administration, about 6 days after administration or about 7 daysor more after administration.

Aspects of the present specification disclose, without limitation, apharmaceutical composition that includes pharmaceutical acceptablecomponents and the pharmaceutical acceptable components is selected fromthe group consisting of a salt, a surfactant, an amino acid, astabilizer or a buffer and the salt is selected from the groupconsisting of citric acid, sodium chloride, potassium chloride, sodiumsulfate, potassium nitrate, sodium phosphate monobasic or sodiumphosphate dibasic, wherein the surfactant can be a polysorbate and thepolysorbate is selected from the group consisting of Tween 20, Tween 80,F68, F88, sorbitain esters, lipids, fatty acids or fatty esters.

Aspects of the present specification disclose, without limitation, atherapeutic compound to treat a appetite reduction is an orexigenic drugand the orexigenic drug can be selected from the group of: alcohol, GHB,and other sedatives such as some benzodiazepine and nonbenzodiazepinetranquilizers and sleeping pills, anti-depressants (some SSRIs,Mianserin, etc.), 5-HT_(2C) receptor antagonists/inverse agonists (e.g.,mirtazapine, mianserin, olanzapine, quetiapine, risperidone,amitriptyline, imipramine, cyproheptadine, etc.), H₁ receptorantagonists/inverse agonists (e.g., buclizine, mirtazapine, mianserin,olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlorpheniraminemaleate, etc.), D₁/D₂ receptor antagonists (e.g., haloperidol,chlorpromazine, olanzapine, risperidone, quetiapine, etc.), Marinol,Megace, Megace ES, α₁-adrenergic receptor antagonists (such asdoxazosin, carvedilol, propanolol, colonidine), Serefam, α₂-adrenergicreceptor agonists (e.g., clonidine, guanfacine, etc.), some betablockers such as propanolol, natural or synthetic CB₁ receptor agonists(e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol,diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodiumvalproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabeticdrugs such as glibenclamide and chlorpropamide, steroids (including,without limitation, boldenone, oxymetholone, dexamethasone, ormethandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone,testosterone), some kappa opioid receptor agonists such as tifluadom,hormones such as mederoxyprogesteronemirtazapine (Remeron), atetracyclic antidepressant; cyproheptadine (Periactin), anantihistamine; nandrolone, oxymetholone, and oxandrolone (Anadrol-50,Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptormodulator (“SARM”), Oxandrin, and other brand names), VT-122 (acoadministration of propranolol and etodolac), type 4 melanocortinreceptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoyreceptor, fast skeletal muscle troponin-activating substance,anticatabolic/anabolic transforming agent MT-102, celecoxib,testosterone, vitamin D, OHR/AVR118, soluble version of the ActRllBreceptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fattyacids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). Inaddition to these prescription drugs, fish oil (eicosapentaenoic acid orEPA), EATMOR, other vitamins and natural or artificial appetitestimulants and cyproheptadine hydrocholoride.

Aspects of the present specification disclose symptoms associated withappetite reduction is reduced by at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least95% and/or the symptoms associated with appetite reduction is reduced byabout 10% to about 100%, about 20% to about 100%, about 30% to about100%, about 40% to about 100%, about 50% to about 100%, about 60% toabout 100%, about 70% to about 100%, about 80% to about 100%, about 10%to about 90%, about 20% to about 90%, about 30% to about 90%, about 40%to about 90%, about 50% to about 90%, about 60% to about 90%, about 70%to about 90%, about 10% to about 80%, about 20% to about 80%, about 30%to about 80%, about 40% to about 80%, about 50% to about 80%, or about60% to about 80%, about 10% to about 70%, about 20% to about 70%, about30% to about 70%, about 40% to about 70%, or about 50% to about 70%and/or the symptoms associated with reduction in the severity ofappetite reduction is reduced by at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90% or at least95% and/or the severity associated with reduction in appetite is reducedby about 10% to about 100%, about 20% to about 100%, about 30% to about100%, about 40% to about 100%, about 50% to about 100%, about 60% toabout 100%, about 70% to about 100%, about 80% to about 100%, about 10%to about 90%, about 20% to about 90%, about 30% to about 90%, about 40%to about 90%, about 50% to about 90%, about 60% to about 90%, about 70%to about 90%, about 10% to about 80%, about 20% to about 80%, about 30%to about 80%, about 40% to about 80%, about 50% to about 80%, or about60% to about 80%, about 10% to about 70%, about 20% to about 70%, about30% to about 70%, about 40% to about 70%, or about 50% to about 70%and/or the treatment for appetite reduction results in an increase inweight by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95% and/or thetreatment for appetite reduction results in an increase in weight byabout 10% to about 100%, about 20% to about 100%, about 30% to about100%, about 40% to about 100%, about 50% to about 100%, about 60% toabout 100%, about 70% to about 100%, about 80% to about 100%, about 10%to about 90%, about 20% to about 90%, about 30% to about 90%, about 40%to about 90%, about 50% to about 90%, about 60% to about 90%, about 70%to about 90%, about 10% to about 80%, about 20% to about 80%, about 30%to about 80%, about 40% to about 80%, about 50% to about 80%, or about60% to about 80%, about 10% to about 70%, about 20% to about 70%, about30% to about 70%, about 40% to about 70%, or about 50% to about 70%and/or the treatment for appetite reduction results in an increase inheight by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95% and/or thetreatment for appetite reduction results in an increase in weight by atleast 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, atleast 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, atleast 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds,at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, atleast 25 pounds, at least 30 pounds, at least 50 pounds. In anotherembodiment, a therapeutic compound disclosed herein for the treatment ofappetite reduction results in an increase in weight by, e.g., from 0.5pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 poundsto 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to tenpounds, from 2 pounds to 7.5 pounds.

Aspects of the present specification disclose a treatment for appetitereduction increases the attentiveness of a patient by at least 10%, atleast 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% or at least 95% and/or increases the attentiveness of apatient by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

Aspects of the present specification disclose a dose of a therapeuticcompound to treat the reduction in appetite is in the range of at least0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, atleast 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/day, atleast 15 mg/kg/day, at least 20 mg/kg/day, at least 25 mg/kg/day, atleast 30 mg/kg/day, at least 35 mg/kg/day, at least 40 mg/kg/day, atleast 45 mg/kg/day, or at least 50 mg/kg/day and/or the dose of thetherapeutic compound to treat reduction in appetite is in the range ofabout 0. 001 mg/kg/day to about 100 mg/kg/day and/or the dose of thetherapeutic compound to treat the reduction in appetite is in the rangeof about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day toabout 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, about0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day to about 30mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100mg/kg/day.

Aspects of the present specification disclose, without limitation, thatthe increase in attentiveness by an individual is measured by CGI-S,wherein the CGI-S scale is from 1 to 7 and a measurement of 7 identifiesan individual that is extremely ill, 6 identifies an individual that isseverely ill, 5 identifies an individual that is markedly ill, 4identifies an individual that is moderately ill, 3 identifies anindividual that is mildly ill, 2 identifies an individual that isborderline ill and a measurement of 1 identifies an individual that isnormal and wherein, the increase in attentiveness measured by CGI-S isby a reduction in the score by 1 or more as compared to a patient notreceiving a therapeutic compound to treat a appetite reduction andwherein, a patient's CGI-S score is reduced by at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90% or at least 95%. Another aspect of the present specificationdiscloses a patient's CGI-S score is reduced by about 10% to about 100%,about 20% to about 100%, about 30% to about 100%, about 40% to about100%, about 50% to about 100%, about 60% to about 100%, about 70% toabout 100%, about 80% to about 100%, about 10% to about 90%, about 20%to about 90%, about 30% to about 90%, about 40% to about 90%, about 50%to about 90%, about 60% to about 90%, about 70% to about 90%, about 10%to about 80%, about 20% to about 80%, about 30% to about 80%, about 40%to about 80%, about 50% to about 80%, or about 60% to about 80%, about10% to about 70%, about 20% to about 70%, about 30% to about 70%, about40% to about 70%, or about 50% to about 70%.

Aspects of the present specification disclose, without limitation, anincrease in attentiveness by an individual is measured by CGI-I wherein,wherein the CGI-I scale is from 1 to 7 and a measurement of 7 identifiesan individual that is very much worse, 6 identifies an individual thatis much worse, 5 identifies an individual that is minimally worse, 4identifies an individual that is no change, 3 identifies an individualthat is minimally improved, 2 identifies an individual that is muchimproved and a measurement of 1 identifies an individual that is verymuch improved and, wherein the increase in attentiveness measured CGI-Iis by a reduction in the score by 1 or more as compared to a patient notreceiving a therapeutic compound to treat a reduction in appetite andfurther, wherein the patient's CGI-S score is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% or at least 95% and further, wherein the patient's CGI-S scoreis reduced by about 10% to about 100%, about 20% to about 100%, about30% to about 100%, about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, about 10% to about 90%, about 20% to about 90%, about 30% to about90%, about 40% to about 90%, about 50% to about 90%, about 60% to about90%, about 70% to about 90%, about 10% to about 80%, about 20% to about80%, about 30% to about 80%, about 40% to about 80%, about 50% to about80%, or about 60% to about 80%, about 10% to about 70%, about 20% toabout 70%, about 30% to about 70%, about 40% to about 70%, or about 50%to about 70%.

Aspects of the present specification disclose an increase inattentiveness by an individual is measured by, without limitation, the pacademic performance rating scale, ADD evaluation scale-3rd edition(ADDES-3), ADHD rating scale-IV (ADHD-RS-IV), youth self report(broadband instrument), Conners parent rating scale-revised (CPRS-R),Conners teacher rating scale-revised (CTRS-R), Conners 3 self-reportingscale (Conner 3-SR; ages 8-18y), home situations questionnaire-revised,inattention/overactivity with aggression (IOWA) Conners teacher's ratingscale, Swanson Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin AglerM-Flynn and Pelham (SKAMP), Vanderbilt ADHD diagnostic parent ratingscale (VADPRS), Vanderbilt ADHD diagnostic teacher rating scale(VADTRS), behavior assessment system for children-2^(nd) edition(BASC-2) or the Conners rating scale long version.

Aspects of the present specification disclose that a psychologicaland/or neurological disorder can be selected from, without limitation,the group of migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and/or tic.

Aspects of the present specification disclose a kit comprising apharmaceutical composition to treat a disorder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts improvement in attention of individuals, for examplechildren, with increased caloric intake.

FIG. 2 depicts the impact of combination treatment on weight.

FIG. 3 depicts the impact of combination treatment on height.

FIG. 4 depicts the change in weight and height for Patient A.

FIG. 5 depicts the ADHD sensitivity for Patient A as measured by CGI-S.

FIG. 6 depicts the change in weight and height for Patient B.

FIG. 7 depicts the ADHD sensitivity for Patient B as measured by CGI-S.

FIG. 8 depicts the change in weight and height for Patient C.

FIG. 9 depicts the ADHD sensitivity for Patient C as measured by CGI-S.

FIG. 10 depicts the change in weight and height for Patient D.

FIG. 11 depicts the ADHD sensitivity for Patient D as measured by CGI-S.

FIG. 12 depicts the change in weight and height for Patient E.

FIG. 13 depicts the ADHD sensitivity for Patient E as measured by CGI-S.

FIG. 14 depicts the change in weight and height for Patient F.

FIG. 15 depicts the ADHD sensitivity for Patient F as measured by CGI-S.

FIG. 16 depicts the change in weight and height for Patient G.

FIG. 17 depicts the ADHD sensitivity for Patient G as measured by CGI-S.

FIG. 18 depicts the change in weight and height for Patient H.

FIG. 19 depicts the ADHD sensitivity for Patient H as measured by CGI-S.

FIG. 20 depicts the impact of combination treatment on the severity ofADHD as measured by CGI-S).

FIG. 21 depicts the impact of treatment on the severity of ADHD asmeasured by CGI-S.

FIG. 22 depicts the impact of treatment on the improvement of ADHD asmeasured by CGI-I.

DETAILED DESCRIPTION OF THE INVENTION

In an embodiment, the present invention discloses the treatment of apsychological and/or neurological disorder. In an embodiment, thepresent invention discloses the treatment of a psychological and/orneurological disorder, including without limitation, attention deficitdisorder, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic, and any other psychological and/or neurologicaldisorder. In an embodiment, the present invention discloses thetreatment of an attention deficit disorder, wherein the attentiondeficit disorder is any disorder that a patient suffers from anattention deficit. In an embodiment, the attention deficit disorder canmanifest as inattentiveness, hyperactivity, impulsiveness,distractibility, disorganization, procrastination, forgetfulness,lethargy, fatigue or any other type of attention deficit disorder. Inanother embodiment, the attention deficit disorder is Attention DeficitHyperactivity Disorder or ADHD.

In an embodiment, the present invention discloses the use of apharmaceutical composition for the treatment of a psychological and/orneurological disorder. In an embodiment, the present invention disclosesthe use of a pharmaceutical composition to treat a psychological and/orneurological disorder, including without limitation, attention deficitdisorder, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic, and any other psychological and/or neurologicaldisorder.

In an embodiment, the present invention discloses the use of apharmaceutical composition for the treatment of ADHD in a patientsuffering from ADHD. In a further embodiment, a pharmaceuticalcomposition treats ADHD in a patient suffering from ADHD and results inweight gain by a patient suffering from ADHD. In another embodiment, apharmaceutical composition treats ADHD in a patient suffering from ADHDand results in the maintenance or an increase of the patient'sattentiveness as compared to an individual not suffering from ADHD andnot taking a pharmaceutical composition to treat ADHD.

Definitions: In describing and claiming the present invention, thefollowing terminology will be used in accordance with the definitionsdescribed below.

“Pharmacologically effective amount,” “physiologically effectiveamount,” and “therapeutically effective amount” are used interchangeablyherein to mean the amount of a drug or drug-combination that is neededto provide a desired level of drug in the bloodstream or in the targettissue. The precise amount will depend upon numerous factors, e.g., theparticular drug or drugs employed, the components and physicalcharacteristics of the therapeutic composition, intended patientpopulation, individual patient considerations, and the like, and canreadily be determined by one skilled in the art, based upon theinformation provided herein.

“Substantially” or “essentially” means nearly totally or completely, forinstance, 95% or greater of some given quantity. For example, asubstantial elimination of one or more symptoms or clinical indicators,means a reduction in severity of 95% or more of a symptom, as assessedby any clinically acceptable method, or an improvement of at least 95%of a given clinical indicator.

A “diminution” of one or more symptoms or clinical indicators, means ameasurable reduction in the severity of such one or more symptoms, asassessed by any clinically acceptable method, or a measurableimprovement of a given clinical indicator, as assessed by a skilledclinician.

The term “patient,” refers to a living organism suffering from or proneto a condition that can be prevented or treated by administration of adrug or combination of drugs of the invention, and includes both humansand animals.

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.

Aspects of the present specification disclose, in part, a pharmaceuticalcomposition. As used herein, the term “pharmaceutical composition” issynonymous with “pharmaceutically acceptable composition” and refers toa therapeutically effective concentration of an active ingredient, suchas, e.g., any of the therapeutic compounds disclosed herein. Apharmaceutical composition disclosed herein is useful for medical andveterinary applications. A pharmaceutical composition may beadministered to an individual alone, or in combination with othersupplementary active ingredients, agents, drugs or hormones.

Aspects of the present specification disclose, in part, a therapeuticcompound. A therapeutic compound is a compound that providespharmacological activity or other direct effect in the diagnosis, cure,mitigation, treatment, or prevention of disease, or to affect thestructure or any function of the body of man or animals. Any suitableform of a therapeutic compound may be chosen. A therapeutic compounddisclosed herein may be used in the form of a pharmaceuticallyacceptable salt, solvate, or solvate of a salt, e.g. the hydrochloride.Additionally, therapeutic compound disclosed herein may be provided asracemates, or as individual enantiomers, including the R- orS-enantiomer. Thus, the therapeutic compound disclosed herein maycomprise an R-enantiomer only, a S-enantiomer only, or a combination ofboth a R-enantiomer and a S-enantiomer of a therapeutic compound. Atherapeutic compound disclosed herein may also be provided as prodrug oractive metabolite.

The present specification discloses combinations of various therapeuticcompounds that when combined produce synergistic effects to treat apatient suffering from a psychological and/or neurological disorder,including, without limitation, attention deficit disorder (including,without limitation ADHD), migraine, anti-serotonergic side effects,narcolepsy, excessive sleepiness associated with shift work, obstructivesleep apnea as an adjunct to continuous positive airways pressure(“CPAP”), exogenous obesity, disruptive behaviour disorder includingoppositional defiant disorder (“ODD”) and conduct disorder (“CD”),obesity, depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic, while stimulating the same patient's appetite. Thefirst step in current treatment of a psychological and/or neurologicaldisorder, including, without limitation, attention deficit disorder(including, without limitation ADHD), migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic, is to usually treat a patient with a short actingstimulant, including, but not limited to an amphetamine and/or amethylheptadine, or introduce a long-acting stimulant, including, butnot limited to a long acting version of an amphetamine ormethylheptadine. If there is insufficient improvement, the dose isgenerally titrated up and/or a long-acting stimulant is initiated inpatients not receiving a long-acting stimulant. If there areside-effects, the dosage can be titrated down or the patient can betaken off the treatment. One of the principal side-effects ofamphetamine and methylphenidate usage is loss of appetite by a patienttaking such medicine. This can have adverse effects on the patient,including, but not limited to, loss of weight, slower or reduced growthin height, reduced attentiveness resulting in a reduction in cognitionand an inability to interact socially. To overcome this it is an aspectof the present invention to provide a method of treatment wherein apatient suffering from a psychological and/or neurological disorder,including, without limitation, attention deficit disorder (including,without limitation ADHD), migraine, anti-serotonergic side effects,narcolepsy, excessive sleepiness associated with shift work, obstructivesleep apnea as an adjunct to continuous positive airways pressure(“CPAP”), exogenous obesity, disruptive behaviour disorder includingoppositional defiant disorder (“ODD”) and conduct disorder (“CD”),obesity, depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic is administered a pharmaceutical composition to treatthe disorder and an appetite stimulant. Through such treatment, apatient will generally gain weight, increase in height, and/or showimproved attentiveness, resulting in an increase in cognition and/or anability to interact socially as compared to the same patient who doesnot take an appetite stimulant.

The present specification discloses combinations of various therapeuticcompounds that when combined produce synergistic effects to treat apatient suffering from ADHD, while stimulating the same patient'sappetite. The first step in current treatment of ADHD is to usuallytreat a patient with a short acting stimulant, including, but notlimited to an amphetamine and/or a methylheptadine, or introduce along-acting stimulant, including, but not limited to a long actingversion of an amphetamine or methylheptadine. Within the first monthfollowing treatment initiation, the patient is generally re-examined forimpact of the treatment on attention and treatment related side effects.If there is insufficient improvement on attention, the dose is generallytitrated up and/or a long-acting stimulant is initiated in patients notreceiving a long-acting stimulant. If there are side-effects, the dosagecan be titrated down or the patient can be taken off the ADHD treatment.One of the principal side-effects of amphetamine and methylphenidateusage is loss of appetite by a patient taking such medicine. This canhave adverse effects on the patient, including, but not limited to, lossof weight, slower or reduced growth in height, reduced attentivenessresulting in a reduction in cognition and an inability to interactsocially. To overcome this it is an aspect of the present invention toprovide a method of treatment wherein a patient suffering from ADHD isadministered a pharmaceutical composition to treat the ADHD and anappetite stimulant. Through such treatment, a patient will generallygain weight, increase in height, and/or show improved attentiveness,resulting in an increase in cognition and/or an ability to interactsocially as compared to the same patient who does not take an appetitestimulant.

In an embodiment, patient side effects are monitored to identify sideeffects associated with the administration of amphetamines and/ormethylphenidate to a patient. In an embodiment, the side effectsgenerally seen in patient's, include without limitation, appetitereduction, resulting in, without limitation, weight loss and/or reducedgrowth, including without limitation, height, loss of attentiveness,including, without limitation, reduced cognition and reduced ability tointeract socially. In a further embodiment, patients found to sufferfrom appetite reduction are provided a pharmaceutical compositioncomprising a therapeutic compound to treat the patient's a psychologicaland/or neurological disorder, including, without limitation, attentiondeficit disorder (including, without limitation ADHD), migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic and atherapeutic compound to treat the patient's appetite reduction. In anembodiment, the therapeutic compound treats both a psychological and/orneurological disorder, including, without limitation, attention deficitdisorder (including, without limitation ADHD), migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, andappetite reduction. In a further embodiment, a therapeutic compoundtreats ADHD and a different therapeutic compound treats appetitereduction. In another embodiment, one or more therapeutic compoundstreat a psychological and/or neurological disorder, including, withoutlimitation, attention deficit disorder (including, without limitationADHD), migraine, anti-serotonergic side effects, narcolepsy, excessivesleepiness associated with shift work, obstructive sleep apnea as anadjunct to continuous positive airways pressure (“CPAP”), exogenousobesity, disruptive behaviour disorder including oppositional defiantdisorder (“ODD”) and conduct disorder (“CD”), obesity, depression(including, without limitation, augmentation of antidepressants intreating refractory depression and cancer-related depression), neuralinsult, fatigue (including, without limitation, disease-related fatiguein patients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and one ormore different therapeutic compounds treat appetite reduction.

In an embodiment, patient side effects are monitored to identify sideeffects associated with the administration of amphetamines and/ormethylphenidate to a patient. In an embodiment, the side effectsgenerally seen in patient's, include without limitation, appetitereduction, resulting in, without limitation, weight loss and/or reducedgrowth, including without limitation, height, loss of attentiveness,including, without limitation, reduced cognition and reduced ability tointeract socially. In a further embodiment, patients found to sufferfrom appetite reduction are provided a pharmaceutical compositioncomprising a therapeutic compound to treat the patient's ADHD and atherapeutic compound to treat the patient's appetite reduction. In anembodiment, the therapeutic compound treats both ADHD and appetitereduction. In a further embodiment, a therapeutic compound treats ADHDand a different therapeutic compound treats appetite reduction. Inanother embodiment, one or more therapeutic compounds treat ADHD and oneor more different therapeutic compounds treat appetite reduction.

A pharmaceutical composition disclosed herein may comprise one or moretherapeutic compounds disclosed herein. In one embodiment, apharmaceutical composition disclosed herein may comprise only a singletherapeutic compound that treats ADHD in a patient while stimulating thepatient's appetite and resulting in an increase in attentiveness. Inanother embodiment, a pharmaceutical composition disclosed herein maycomprise a plurality of therapeutic compounds wherein one or more of thetherapeutic compounds treat ADHD in a patient, while one or more of thetherapeutic compounds stimulates the patient's appetite and results inan increase in attentiveness. In aspects of this embodiment, apharmaceutical composition disclosed herein comprises at least onetherapeutic compound that treats ADHD in a patient while stimulating thepatient's appetite resulting in an increase in attentiveness, at leasttwo therapeutic compounds wherein one or more of the therapeuticcompounds treats ADHD in a patient while one or more of the therapeuticcompounds stimulates the patient's appetite resulting in an increase inattentiveness, at least three therapeutic compounds wherein one or moreof the therapeutic compounds treats ADHD in a patient while one or moreof the therapeutic compounds stimulates the patient's appetite resultingin an increase in attentiveness, or at least four therapeutic compoundswherein one or more of the therapeutic compounds treats ADHD in apatient while one or more of the therapeutic compounds stimulates thepatient's appetite resulting in an increase in attentiveness. In otheraspects of this embodiment, a pharmaceutical composition disclosedherein comprises at most two therapeutic compounds wherein one or moreof the therapeutic compounds treats ADHD in a patient while one or moreof the therapeutic compounds stimulates the patient's appetite resultingin an increase in attentiveness, at most three therapeutic compoundswherein one or more of the therapeutic compounds treats ADHD in apatient while one or more of the therapeutic compounds stimulates thepatient's appetite resulting in an increase in attentiveness, or at mostfour therapeutic compounds wherein one or more of the therapeuticcompounds treats ADHD in a patient while one or more of the therapeuticcompounds stimulates the patient's appetite resulting in an increase inattentiveness. In yet other aspects of this embodiment, a pharmaceuticalcomposition disclosed herein comprises one to three therapeuticcompounds wherein one or more of the therapeutic compounds treats ADHDin a patient while one or more of the therapeutic compounds stimulatesthe patient's appetite resulting in an increase in attentiveness, two tofour therapeutic compounds wherein one or more of the therapeuticcompounds treats ADHD in a patient while one or more of the therapeuticcompounds stimulates the patient's appetite resulting in an increase inattentiveness, two to five therapeutic compounds wherein one or more ofthe therapeutic compounds treats ADHD in a patient while one or more ofthe therapeutic compounds stimulates the patient's appetite resulting inan increase in attentiveness, three to five therapeutic compoundswherein one or more of the therapeutic compounds treats ADHD in apatient while one or more of the therapeutic compounds stimulates thepatient's appetite resulting in an increase in attentiveness, or two tothree therapeutic compounds wherein one or more of the therapeuticcompounds treats ADHD in a patient while one or more of the therapeuticcompounds stimulates the patient's appetite resulting in an increase inattentiveness. In aspects of this embodiment, a therapeutic compoundthat treats ADHD in a patient and/or stimulates the patient's.

In another embodiment, a pharmaceutical composition disclosed herein totreat a patient suffering from ADHD include, without limitation,amphetamines and/or methylphenidate. In an embodiment, a pharmaceuticalcomposition disclosed herein to treat a patient suffering from ADHDinclude, without limitation, OROS methylphenidate (Concerta),dextroamphetamine immediate/sustained release (Adderall/Adderall XR),dexmethylphenidate (Focalin), Focalin XR, Metadate CD, Metadate ER,NWP09, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Spansules,Methylin ER (Ritalin SR), methylphenidate (Ritalin), and methylphenidateCR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv ER,Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch,Methylin chewable, Methylin liquid, Dextrostat, Strattera, Tenex,Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil,Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor,Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor,Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol,Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane,Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, XanaxXR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata,Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol,Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compoundsidentified in Table 1.

In another embodiment, a pharmaceutical composition disclosed herein totreat a patient suffering from a psychological and/or neurologicaldisorder, including without limitation, migraine, anti-serotonergic sideeffects and narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic include, without limitation, amphetamines and/ormethylphenidate. In an embodiment, a pharmaceutical compositiondisclosed herein to treat a patient suffering from a psychologicaland/or neurological disorder, including without limitation, migraine,anti-serotonergic side effect and narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic include,without limitation, OROS methylphenidate (Concerta), dextroamphetamineimmediate/sustained release (Adderall/Adderall XR), dexmethylphenidate(Focalin), Focalin XR, Metadate CD, dextroamphetamine (Dexedrine),Dexedrine Spansules, Methylin ER (Ritalin SR), methylphenidate(Ritalin), and methylphenidate CR, Ritalin, Ritalin LA, Methylinchewable, Methylin liquid, Daytrana Patch, SD-483, SPD-503, Ritalin SR,Intuniv ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay,Metadate ER, NWP09, Dexedrine, bupropion, Dextrostat, Strattera, Tenex,Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil,Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor,Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor,Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol,Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane,Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, XanaxXR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata,Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol,Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compoundsidentified in Table 1.

TABLE 1 Brand Name Generic Name** Ritalin methylphenidate Ritalin SRRitalin LA Concerta Daytrana Equasym XL Focalin Methylin MethylinChewable Methylin Liquid Metadate CD Metadate ER NWP09 Concertamethylphenidate Focalin Focalin XR Metadate CD Ritalin LA Daytrana PatchDexedrine amphetamine Dexedrine Spansule Dextrostat Adderall SD-483Adderall XR amphetamine salts Strattera atomoxetine Tenex guanfacineSPD-503 Intuniv ER Intuniv Catapres clonidine Catapres TTS patch DixiritKapvay Prozac fluoxetine Serefam Zoloft sertraline Luvox fluvoxaminePaxil paroxetine Paxil Cr Pexeva Celexa citalopram Lexapro escitalopramTofranil imipramine Tofranil-PM Norpramin desipramine Elavilamitryptyline Pamelor nortriptyline Sinequan doxepin Anafranilclomipramine Wellbutrin bupropion Wellbutrin SR Wellbutrin XL BudeprionSR Budeprion XL Aplenzin Effexor venlafaxine Effexor XR venlafaxineRemeron mirtazapine Cymbalta duloxetine Nardil phenelzine Parnatetranylcypromine Emsam patch selegiline Haldol haloperidol Orap pimozideProlixin fluphenazine Mellaril thioridazine Thorazine chlorpromazineStelazine trifluoperazine Moban molindone Loxitane loxapine Risperdalrisperidone Zyprexa olanzapine Seroquel quetiapine Geodon ziprasidoneAbilify aripiprazole Clozaril clozapine Xanax alprazolam Xanax XRKlonopin clonazepam Ativan lorazepam Buspar buspirone Ambien zolpidemAmbien CR Lunesta eszopiclone Sonata zaleplon Rozerem ramelteon Lithiumlithium Lithobid Eskalith Depakote divalproex valproate Tegretolcarbamazepine Carbatrol Epitol Tegretol XR Generics Tegretol EquetroTrileptal oxcarbazepine Lamictal lamotrigine Topamax topiramateNeurontin gabapentin Lobeline active ingredient in the lobelia planttargets nicotinic receptors Unnamed supplement zinc, magnesium, vitaminB6 and vitamin C Cylert central nervous system stimulant CX-1739ampakine CX-2076 ampakine CX-516 ampakine CX-546 ampakine CX-614ampakine CX-717 ampakine ABT-894 atomoxetine Strattera atomoxetineSON0216 bifemelane Alnert Celeport OPC-34712 Dopamine D2 receptorpartial agonist Procentra dextroamphetamine Vyvanse lisdexamfetaminelisdexamfetamine Various melatonin Namenda memantine Desoxynmethamphetamine Savella milnacipran Attenace modafinil Provigil ABT-894neuronal nicotinic receptor AZD1446 AZD3480 TC-5619 ABT-089 TD-9855norepinephrine (and serotonin) reuptake LY2216684 receptor Desipraminenorpramin Pamelor nortriptyline Cyclert pemoline KP106 prodrug ofd-amphetamine Nuvigil R modafinil Kuvan sapropterin SGS-742 SelectiveGABA-B receptor antagonist Eltoprazine Serotonin 5-HT1A and 5-HT1Breceptor agonist DOV-102 Serontoin-norepinephrine-dopamine reuptakeDOV-677 inhibitor Zoloft sertraline Chantix varenicline Orazinc zincZinc sulfate IV Zine sulfate

A therapeutic compound disclosed herein may be an orexigenic drug. Asused herein, the term orexigenic drug refers to a class of therapeuticcompounds that have the ability to stimulate a patient's appetite.Examples of suitable orexigenic drugs include, without limitation,alcohol, GHB, and other sedatives such as some benzodiazepine andnonbenzodiazepine tranquilizers and sleeping pills, anti-depressants(some SSRIs, Mianserin, etc.), 5-HT_(2C) receptor antagonists/inverseagonists (e.g., mirtazapine, mianserin, olanzapine, quetiapine,risperidone, amitriptyline, imipramine, cyproheptadine, etc.), H₁receptor antagonists/inverse agonists (e.g., buclizine, mirtazapine,mianserin, olanzapine, quetiapine, n-3 fatty acids, amitriptyline,chlorpheniramine maleate, etc.), D₁/D₂ receptor antagonists (e.g.,haloperidol, chlorpromazine, olanzapine, risperidone, quetiapine, etc.),Marinol, Megace, Megace ES, α₁-adrenergic receptor antagonists (such asdoxazosin, carvedilol, propanolol, colonidine), Serefam, α₂-adrenergicreceptor agonists (e.g., clonidine, guanfacine, etc.), some betablockers such as propanolol, natural or synthetic CB₁ receptor agonists(e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol,diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodiumvalproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabeticdrugs such as glibenclamide and chlorpropamide, steroids (including,without limitation, boldenone, oxymetholone, dexamethasone, ormethandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone,testosterone), some kappa opioid receptor agonists such as tifluadom,hormones such as mederoxyprogesterone.

Additional therapeutic compounds that are examples of suitableorexigenic drugs, include, without limitation, mirtazapine (Remeron), atetracyclic antidepressant; cyproheptadine (Periactin), anantihistamine; nandrolone, oxymetholone, and oxandrolone (Anadrol-50,Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptormodulator (“SARM”), Oxandrin, and other brand names), VT-122 (acoadministration of propranolol and etodolac), type 4 melanocortinreceptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoyreceptor, fast skeletal muscle troponin-activating substance,anticatabolic/anabolic transforming agent MT-102, celecoxib,testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIBreceptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fattyacids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). Inaddition to these prescription drugs, fish oil (eicosapentaenoic acid orEPA), EATMOR, other vitamins and natural or artificial appetitestimulants.

In an embodiment, the orexigenic drug is cyproheptadine hydrochloride(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidinehydrochloride) (“Cyproheptadine”). Cyproheptadine is used as an oralmonotherapy for allergy under the tradename Periactin®. Cyproheptadinereaches peak plasma levels in 1-3 hours and has a half-life of 8 hours.(Gunja, 2004). In the 1960s, it was recognized that a side-effect ofCyproheptadine was it could cause weight gain and drowsiness, whichprompted the development of newer anti-histamines with better sideeffect profiles. In an embodiment, a pharmaceutical composition iscomprised of a therapeutic compound for the treatment of ADHD andCyproheptadine. In a further embodiment, a pharmaceutical composition iscomprised of an amphetamine and/or methylphenidate and Cyproheptadine.In another embodiment, a pharmaceutical compound is comprised of eitherRitalin, Focalin or Concerta and Cyproheptadine.

The present specification discloses combinations of various therapeuticcompounds that when combined produce synergistic effects in treating apatient suffering from ADHD and/or a psychological and/or neurologicaldisorder, including without limitation, migraine, anti-serotonergic sideeffects and narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic, while maintaining the patient's appetite andconcomitant attentiveness. In addition, the present specificationdiscloses that administration of the disclosed combinations of atherapeutic compound can be through inhalation, oral administration,intravenous (“IV”), intranasal (“IN”), sublingual, subcutaneous (“SC”),enteral, parenteral, inhaled, transcutaneous TC (for example, withoutlimitation, through a patch placed on the skin of an individual beingtreated), rectal and/or vaginal.

In an embodiment, the patient is administered or takes takes aserotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), or triplereuptake inhibitor (TRI), one or more times a day. A SNDRI or TRI is adrug/ligand that simultaneously acts as a reuptake inhibitor for themonoamine neurotransmitters, serotonin (5-HT), norepinephrine(noradrenaline, NA) and dopamine (DA). In an embodiment, a SNDRI or TRIis, without limitation, EB-1020, which is catecholamine preferring TUI,is a triple reuptake inhibitor that modulates norepinephrine (NE),dopamine (DA) and serotonin (5-HT) in a ratio of 1 to 6 to 14,respectively. This preferential NE with moderate DA reuptake inhibitionprofile, with a small amount of 5-HT reuptake inhibition, has thepotential to be an effective treatment for ADHD in adults with less riskof drug abuse liability and diversion than the stimulants used for ADHDtoday.

In an embodiment, the patient is administered or takes a pharmaceuticalcomposition two or more times per day, wherein the pharmaceuticalcomposition comprises a therapeutic compound for the treatment of ADHDand/or a psychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects and narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic and an appetite stimulant. In an embodiment, thepatient is administered or takes a pharmaceutical composition once aday, wherein the pharmaceutical composition comprises a therapeuticcompound for the treatment of ADHD and/or a psychological and/orneurological disorder, including without limitation, migraine,anti-serotonergic side effects narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic, and anappetite stimulant. In an embodiment, the patient is administered ortakes a pharmaceutical composition in the morning or afternoon, whereinthe pharmaceutical composition comprises a therapeutic compound for thetreatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effectsand narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic and an appetite stimulant. In another embodiment, thepatient is administered or takes a pharmaceutical composition in themorning, wherein the pharmaceutical composition comprises a therapeuticcompound for the treatment of ADHD and/or a psychological and/orneurological disorder, including without limitation, migraine,anti-serotonergic side effects and narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic and anappetite stimulant. In another embodiment, the patient is administeredor takes a pharmaceutical composition in the afternoon, wherein thepharmaceutical composition comprises a therapeutic compound for thetreatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effectsand narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic and an appetite stimulant. In another embodiment, thepatient does not take a pharmaceutical composition in the evening orbefore bed, wherein the pharmaceutical composition comprises atherapeutic compound for the treatment of ADHD and/or a psychologicaland/or neurological disorder, including without limitation, migraine,anti-serotonergic side effects narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy , bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD, tic and anappetite stimulant. In a further embodiment, the patient taking apharmaceutical composition comprising a therapeutic compound for thetreatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effectsand narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic and an appetite stimulant in the morning eithermaintains or increases their attentiveness when compared to a patienttaking only a therapeutic compound for the treatment of ADHD and/or apsychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic. In a further embodiment, the patient taking apharmaceutical composition comprising a therapeutic compound for thetreatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effectsand narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD, tic and an appetite stimulant in the afternoon eithermaintains or increases their attentiveness when compared to a patienttaking only a therapeutic compound for the treatment of ADHD and/or apsychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic.

In an embodiment, attentiveness is measured using the Clinical GlobalImpression rating scales to measure symptom severity, treatment responseand the efficacy of treatments in treatment studies of patients withmental disorders (Guy, W., 1976). In an embodiment, attentiveness ismeasure using the Clinical Global Impression-Severity scale (“CGI-S”).In an embodiment, CGI-S is a 7-point scale that requires the clinicianto rate the severity of the patient's illness at the time of assessment,relative to the clinician's past experience with patients who have thesame diagnosis. Considering total clinical experience, a patient isassessed on severity of mental illness at the time of rating 1, normal,not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderatelyill; 5, markedly ill; 6, severely ill; or 7, extremely ill. In anembodiment, attentiveness is measured using the Clinical GlobalImpression-Improvement scale (“CGI-I”). CGI-I is a 7 point scale thatrequires the clinician to assess how much the patient's illness hasimproved or worsened relative to a baseline state at the beginning ofthe intervention and rated as: 1, very much improved; 2, much improved;3, minimally improved; 4, no change; 5, minimally worse; 6, much worse;or 7, very much worse. In an embodiment, attentiveness is measured usingthe Clinical Global Impression-Efficacy Index (“CGI-E”). CGI-E is a 4point x 4 point rating scale that assesses the therapeutic effect of thetreatment as 1, unchanged to worse; 2, minimal; 3, moderate; 4, markedby side effects rated as none, do not significantly interfere withpatient's functioning, significantly interferes with patient'sfunctioning and outweighs therapeutic effect.

In a further embodiment, attentiveness is measured using one or more ofthe following ADHD screening tools and rating scales for children andadolescents, including, without limitation, academic performance ratingscale, ADD evaluation scale-3^(rd) edition (ADDES-3), ADHD ratingscale-IV (ADHD-RS-IV), youth self report (broadband instrument), Connersparent rating scale-revised (CPRS-R), Conners teacher ratingscale-revised (CTRS-R), Connoers 3 self-reporting scale (Conner 3-SR;ages 8-18y), home situations questionnaire-revised,inattention/overactivity with aggression (IOWA) Conners teacher's ratingscale, Swanson Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin AglerM-Flynn and Pelham (SKAMP). Vanderbilt ADHD diagnostic parent ratingscale (VADPRS), Vanderbilt ADHD diagnostic teacher rating scale(VADTRS), behavior assessment system for children-2^(nd) edition(BASC-2). In an embodiment, attentiveness is measured by the Connersrating scale long version which includes without limitation, thesesubscales:

Oppositional Social Problems Cognitive Problems/InattentionPsychosomatic Hyperactivity Conners Global Index Anxious-Shy DSM-IVSymptom Subscale Perfectionism ADHD Index

In one embodiment, a therapeutic compound disclosed herein is used forthe treatment of ADHD and/or a psychological and/or neurologicaldisorder, including without limitation, migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic. In aspects of this embodiment, a therapeuticcompound for the treatment of ADHD and/or a psychological and/orneurological disorder, including without limitation, migraine,anti-serotonergic side effects and narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and tic, reducesa symptom or set of symptoms, including, without limitation, the CGI-Sindex associated with ADHD and/or a psychological and/or neurologicaldisorder, including without limitation, migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, by, e.g., at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90% or at least95%. In other aspects of this embodiment, a therapeutic compound for thetreatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effectsand narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression fibromyalgia and hepatitis C),lethargy, binge eating disorder, schizophrenia, sleep cycle disorder,cocaine addiction, Parkinson's Disease, combat and non-combat relatedPTSD and tic, reduces a symptom associated with ADHD and/or apsychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects and narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, by, e.g., about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

In one embodiment, a therapeutic compound disclosed herein is used forthe treatment of appetite reduction. In aspects of this embodiment, atherapeutic compound for the treatment of ADHD and/or a psychologicaland/or neurological disorder, including without limitation, migraine,anti-serotonergic side effects and narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and tic, reducesa symptom associated with appetite reduction by, e.g., at least 10%, atleast 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% or at least 95%. In other aspects of this embodiment, atherapeutic compound for the treatment of appetite reduction reduces asymptom associated with appetite reduction by, e.g., about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%.

In another embodiment, a therapeutic compound disclosed herein for thetreatment of ADHD reduces the severity of ADHD in a patient. In aspectsof this embodiment, a therapeutic compound for the treatment of ADHDreduces the severity of ADHD in a patient by, e.g., at least 10%, atleast 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% or at least 95%. In other aspects of this embodiment, atherapeutic compound for the treatment of ADHD reduces the severity ofADHD in a patient by, e.g., about 10% to about 100%, about 20% to about100%, about 30% to about 100%, about 40% to about 100%, about 50% toabout 100%, about 60% to about 100%, about 70% to about 100%, about 80%to about 100%, about 10% to about 90%, about 20% to about 90%, about 30%to about 90%, about 40% to about 90%, about 50% to about 90%, about 60%to about 90%, about 70% to about 90%, about 10% to about 80%, about 20%to about 80%, about 30% to about 80%, about 40% to about 80%, about 50%to about 80%, or about 60% to about 80%, about 10% to about 70%, about20% to about 70%, about 30% to about 70%, about 40% to about 70%, orabout 50% to about 70%.

In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction reduces the severity of appetitereduction in a patient. In aspects of this embodiment, a therapeuticcompound for the treatment of appetite reduction reduces the severity ofappetite reduction in a patient by, e.g., at least 10%, at least 15%, atleast 20%, at least 25%, at least 30%, at least 35%, at least 40%, atleast 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90% or atleast 95%. In other aspects of this embodiment, a therapeutic compoundfor the treatment of appetite reduction reduces the severity of appetitereduction in a patient by, e.g., about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction results in an increase in weight by,e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least30%, at least 35%, at least 40%, at least 45%, at least 50%, at least55%, at least 60%, at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90% or at least 95%. In other aspects ofthis embodiment, a therapeutic compound for the treatment of appetitereduction results in an increase in weight by, e.g., about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%.

In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction results in an increase in height by,e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least30%, at least 35%, at least 40%, at least 45%, at least 50%, at least55%, at least 60%, at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90% or at least 95%. In other aspects ofthis embodiment, a therapeutic compound for the treatment of appetitereduction results in an increase in height by, e.g., about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%

In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction results in an increase in weight by,e.g., at least 0.5 pounds, at least 1 pound, at least 1.5 pounds, atleast 2 pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5pounds, at least 4 pounds, at least 4.5 pounds, at least 5 pounds, atleast 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 pounds, atleast 9 pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5pounds, at least 11 pounds, at least 11.5 pounds, at least 12 pounds, atleast 12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, atleast 25 pounds, at least 30 pounds, at least 50 pounds. In anotherembodiment, a therapeutic compound disclosed herein for the treatment ofappetite reduction results in an increase in weight by, e.g., from 0.5pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 poundsto 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to tenpounds, from 2 pounds to 7.5 pounds.

In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction increases the attentiveness of a patientbeing treated for ADHD and/or a psychological and/or neurologicaldisorder, including without limitation, migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic. In aspects of this embodiment, a therapeuticcompound for the treatment of appetite reduction increases theattentiveness of a patient being treated for ADHD or a psychologicaland/or neurological disorder, including without limitation, migraine,anti-serotonergic side effects and narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and tic, by,e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least30%, at least 35%, at least 40%, at least 45%, at least 50%, at least55%, at least 60%, at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90% or at least 95%. In other aspects ofthis embodiment, a therapeutic compound for the treatment of appetitereduction increases the attentiveness of a patient being treated forADHD and/or a psychological and/or neurological disorder, includingwithout limitation, migraine, anti-serotonergic side effects andnarcolepsy, excessive sleepiness associated with shift work, obstructivesleep apnea as an adjunct to continuous positive airways pressure(“CPAP”), exogenous obesity, disruptive behaviour disorder includingoppositional defiant disorder (“ODD”) and conduct disorder (“CD”),obesity, depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, by, e.g., about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

In an embodiment, a pharmaceutical composition disclosed herein mayoptionally include a pharmaceutically-acceptable carrier thatfacilitates processing of an active ingredient intopharmaceutically-acceptable compositions. As used herein, the term“pharmacologically-acceptable carrier” is synonymous with“pharmacological carrier” and means any carrier that has substantiallyno long term or permanent detrimental effect when administered andencompasses terms such as “pharmacologically acceptable vehicle,stabilizer, diluent, additive, auxiliary or excipient.” Such a carriergenerally is mixed with an active compound or permitted to dilute orenclose the active compound and can be a solid, semi-solid, or liquidagent. It is understood that the active ingredients can be soluble orcan be delivered as a suspension in the desired carrier or diluent. Anyof a variety of pharmaceutically acceptable carriers can be usedincluding, without limitation, aqueous media such as, withoutlimitation, water, saline, glycine, hyaluronic acid and the like; solidcarriers such as, without limitation, mannitol, lactose, starch,magnesium stearate, sodium saccharin, talcum, cellulose, glucose,sucrose, magnesium carbonate, and the like; solvents; dispersion media;coatings; antibacterial and antifungal agents; isotonic and absorptiondelaying agents; or any other inactive ingredient. Selection of apharmacologically acceptable carrier can depend on the mode ofadministration. Except insofar as any pharmacologically acceptablecarrier is incompatible with the active ingredient, its use inpharmaceutically acceptable compositions is contemplated. Non-limitingexamples of specific uses of such pharmaceutical carriers can be foundin Pharmaceutical Dosage Forms and Drug Delivery Systems (Howard C.Ansel et al., eds., Lippincott Williams & Wilkins Publishers, 7th ed.1999); REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY (Alfonso R.Gennaro ed., Lippincott, Williams & Wilkins, 20th ed. 2000); Goodman &Gilman's The Pharmacological Basis of Therapeutics (Joel G. Hardman etal., eds., McGraw-Hill Professional, 10th ed. 2001); and Handbook ofPharmaceutical Excipients (Raymond C. Rowe et al., APhA Publications,4th edition 2003). These protocols are routine procedures and anymodifications are well within the scope of one skilled in the art andfrom the teaching herein.

In an embodiment, a pharmaceutical composition disclosed herein canoptionally include, without limitation, other pharmaceuticallyacceptable components (or pharmaceutical components), including, withoutlimitation, buffers, preservatives, tonicity adjusters, salts,antioxidants, osmolality adjusting agents, physiological substances,pharmacological substances, bulking agents, emulsifying agents, wettingagents, flavoring agents, coloring agents, and the like. In anembodiment, various buffers and means for adjusting pH can be used toprepare a pharmaceutical composition disclosed herein, provided that theresulting preparation is pharmaceutically acceptable. Such buffersinclude, without limitation, acetate buffers, citrate buffers, phosphatebuffers, neutral buffered saline, phosphate buffered saline and boratebuffers. It is understood that acids or bases can be used to adjust thepH of a composition as needed. In an embodiment, pharmaceuticallyacceptable antioxidants include, without limitation, sodiummetabisulfite, sodium thiosulfate, acetylcysteine, butylatedhydroxyanisole and butylated hydroxytoluene. Useful preservativesinclude, without limitation, benzalkonium chloride, chlorobutanol,thimerosal, phenylmercuric acetate, phenylmercuric nitrate, a stabilizedoxy chloro composition and chelants, such as, e.g., DTPA orDTPA-bisamide, calcium DTPA, and CaNaDTPA-bisamide. In an embodiment,tonicity adjustors useful in a pharmaceutical composition include,without limitation, salts such as, e.g., sodium chloride, potassiumchloride, mannitol or glycerin and other pharmaceutically acceptabletonicity adjustor. In an embodiment, the pharmaceutical composition maybe provided as a salt and can be formed with many acids, including butnot limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, malic,succinic, etc. Salts tend to be more soluble in aqueous or otherprotonic solvents than are the corresponding free base forms. It isunderstood that these and other substances known in the art ofpharmacology can be included in a pharmaceutical composition.

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may be formulatedfor either local or systemic delivery using topical, enteral orparenteral routes of administration. In an additional embodiment, atherapeutic compound disclosed herein may be formulated by itself in apharmaceutical composition, or may be formulated together with one ormore other therapeutic compounds disclosed herein in a singlepharmaceutical composition.

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may be made into aninhaled formulation. In an embodiment, inhaled formulations suitable forenteral or parenteral administration include, without limitation,aerosols, dry powders. In an additional embodiment, a therapeuticcompound or composition disclosed herein intended for suchadministration may be prepared according to any method known to the artfor the manufacture of pharmaceutical compositions.

In an embodiment, such inhaled dosage forms, the therapeutic compoundmay be prepared for delivery as an aerosol in a liquid propellant foruse in a pressurised (PDI) or other metered dose inhaler (MDI). In anembodiment, propellants suitable for use in a PDI or MDI include,without limitation, CFC-12, HFA-134a, HFA-227, HCFC-22(difluorochloromethane), HFA-152 (difluoroethane and isobutane). In anembodiment, a therapeutic compound may also be delivered using anebulisers or other aerosol delivery system. In an embodiment, atherapeutic compound may be prepared for delivery as a dry powder foruse in a dry powder inhaler (DPI). In an embodiment, a dry powder foruse in the inhalers will usually have a mass median aerodynamic diameterof less than 100 pm, 90 pm, 80 pm, 70 pm, 60 pm 50 pm, 40 pm, 30 pm, 20pm and 10 pm. In an embodiment, microparticles having aerodynamicdiameters in the range of about 5 pm to about 0.5 pm will generally bedeposited in the respiratory bronchioles, whereas smaller particles,having aerodynamic diameters in the range of about 2 pm to about 0.05pm, are likely to be deposited in the alveoli. In an embodiment, a DPImay be a passive delivery mechanism, which relies on the individual'sinspiration to introduce the particles into the lungs, or an activedelivery mechanism, requiring a mechanism for delivering the powder tothe individual. In an embodiment, a therapeutically effective amount ofa therapeutic compound disclosed herein for an inhaled formulation maybe between about 0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) toabout 80% (w/v), 0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) toabout 60% (w/v), 0.0001% (w/v) to about 50% (w/v), 0.0001% (w/v) toabout 40% (w/v), 0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) toabout 20% (w/v), 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) toabout 90.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) toabout 70.0% (w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% (w/v) toabout 0.0% (w/v), 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) toabout 30.0% (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) toabout 10.0% (w/v) or about 0.01% (w/v) to about 90.0% (w/v), about 0.01%(w/v) to about 80.0% (w/v), about 0.01% (w/v) to about 70.0% (w/v),about 0.01% (w/v) to about 60.0% (w/v), about 0.01% (w/v) to about 50.0%(w/v), about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) toabout 30.0% (w/v)about 0.01% (w/v) to about 20.0% (w/v) or about 0.01%(w/v) to about 10.0% (w/v). In an embodiment, an inhaled formulations, atherapeutically effective amount of a therapeutic compound disclosedherein for an inhaled formulation may also be between 0.0001% (w/v) toabout 90% (w/v), 0.0001% (w/v) to about 80% (w/v), 0.0001% (w/v) toabout 70% (w/v), 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) toabout 50% (w/v), 0.0001% (w/v) to about 40% (w/v), 0.0001% (w/v) toabout 30% (w/v), 0.0001% (w/v) to about 20% (w/v), 0.0001% (w/v) toabout 10% (w/v), about 0.001% (w/v) to about 90.0% (w/v), 0.001% (w/v)to about 80.0% (w/v), 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) toabout 60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% (w/v) toabout 40.0% (w/v), 0.001% (w/v) to about 30.0% (w/v), 0.001% (w/v) toabout 20.0% (w/v), 0.001% (w/v) to about 10.0% (w/v) or about 0.01%(w/v) to about 90.0% (w/v), about 0.01% (w/v) to about 80.0% (w/v),about 0.01% (w/v) to about 70.0% (w/v), about 0.01% (w/v) to about 60.0%(w/v), about 0.01% (w/v) to about 50.0% (w/v), about 0.01% (w/v) toabout 40.0% (w/v), about 0.01% (w/v) to about 30.0% (w/v)about 0.01%(w/v) to about 20.0% (w/v) or about 0.01% (w/v) to about 10.0% (w/v).

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may be made into asolid formulation. In an embodiment, a solid formulations suitable forenteral or parenteral administration include, without limitation,capsules, tablets, pills, troches, lozenges, orally dissolving strips,powders and granules suitable for inhalation or for reconstitution intosterile injectable solutions or dispersions. In an embodiment, each ofthe aforementioned formulations can include, without limitation, animmediate release formulation, a slow release formulation (includingwithout limitation, a wax matrix), beaded (including, withoutlimitation, a double beaded wherein a bead releases immediately followedby another bead releasing at a later time), spheroidal oral drugabsorption system (“SODAS”), an oral release osmotic system (“OROS”),chewable tablet, a patch (including, without limitation, a deliveryoptimized thermodynamics (“DOT”)), sprinkles, or a prodrug. In anembodiment, a therapeutic compound or composition disclosed hereinintended for such administration may be prepared according to any methodknown to the art for the manufacture of pharmaceutical compositions. Inan embodiment, such solid dosage forms, the therapeutic compound may beadmixed without limitation (a) at least one inert customary excipient(or carrier), such as without limitation, sodium citrate or dicalciumphosphate or (b) fillers or extenders, as for example, withoutlimitation, starch, lactose, sucrose, glucose, mannitol, isomalt, andsilicic acid, (c) binders, such as, without limitation,carboxymethylcellulose, alignates, gelatin, polyvinylpyrrolidone,sucrose and acacia, (d) humectants, such as, e.g., glycerol, (e)disintegrating agents, such as, without limitation, agar-agar, calciumcarbonate, corn starch, potato starch, tapioca starch, alginic acid,certain complex silicates and sodium carbonate, (f) solution retarders,such as, without limitation, paraffin, (g) absorption accelerators, suchas, without limitation, quaternary ammonium compounds, (h) wettingagents, such as, without limitation, cetyl alcohol and glycerolmonostearate, (i) adsorbents, such as, without limitation, kaolin andbentonite, (j) lubricants, such as, without limitation, talc, stearicacid, calcium stearate, magnesium stearate, solid polyethylene glycols,sodium lauryl sulfate or mixtures thereof, and (k) buffering agents. Inan embodiment, the tablets may be uncoated or they may be coated byknown techniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period. In an additional embodiment, without limitation, a timedelay material such as glyceryl monostearate or glyceryl distearate maybe employed. In an embodiment, in solid formulations, a therapeuticallyeffective amount of a therapeutic compound disclosed herein typicallymay be between about 0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) toabout 80% (w/v), 0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) toabout 60% (w/v), 0.0001% (w/v) to about 50% (w/v), 0.0001% (w/v) toabout 40% (w/v), 0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) toabout 20% (w/v), 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) toabout 90.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) toabout 70.0% (w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% (w/v) toabout 0.0% (w/v), 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) toabout 30.0% (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) toabout 10.0% (w/v) or about 0.01% (w/v) to about 90.0% (w/v), about 0.01%(w/v) to about 80.0% (w/v), about 0.01% (w/v) to about 70.0% (w/v),about 0.01% (w/v) to about 60.0% (w/v), about 0.01% (w/v) to about 50.0%(w/v), about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) toabout 30.0% (w/v)about 0.01% (w/v) to about 20.0% (w/v) or about 0.01%(w/v) to about 10.0% (w/v).

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may be made into asemi-solid formulation. In an embodiment, a semi-solid formulationssuitable for topical administration include, without limitation,ointments, creams, salves, and gels. In an embodiment, a therapeuticcompound or composition disclosed herein intended for suchadministration may be prepared according to any method known to the artfor the manufacture of pharmaceutical compositions. In an embodiment, insemi-solid formulations, a therapeutically effective amount of atherapeutic compound disclosed herein typically may be between about0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) to about 80% (w/v),0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) to about 60% (w/v),0.0001% (w/v) to about 50% (w/v), 0.0001% (w/v) to about 40% (w/v),0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) to about 20% (w/v),0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) to about 90.0%(w/v), 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) to about 70.0%(w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% (w/v) to about 0.0%(w/v), 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) to about 30.0%(w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) to about 10.0%(w/v) or about 0.01% (w/v) to about 90.0% (w/v), about 0.01% (w/v) toabout 80.0% (w/v), about 0.01% (w/v) to about 70.0% (w/v), about 0.01%(w/v) to about 60.0% (w/v), about 0.01% (w/v) to about 50.0% (w/v),about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) to about 30.0%(w/v)about 0.01% (w/v) to about 20.0% (w/v) or about 0.01% (w/v) toabout 10.0% (w/v). In an embodiment, in semi-solid formulations, atherapeutically effective amount of a therapeutic compound disclosedherein typically may also be between about 0.0001% (w/v) to about 90%(w/v), 0.0001% (w/v) to about 80% (w/v), 0.0001% (w/v) to about 70%(w/v), 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) to about 50%(w/v), 0.0001% (w/v) to about 40% (w/v), 0.0001% (w/v) to about 30%(w/v), 0.0001% (w/v) to about 20% (w/v), 0.0001% (w/v) to about 10%(w/v), about 0.001% (w/v) to about 90.0% (w/v), 0.001% (w/v) to about80.0% (w/v), 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to about60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% (w/v) to about40.0% (w/v), 0.001% (w/v) to about 30.0% (w/v), 0.001% (w/v) to about20.0% (w/v), 0.001% (w/v) to about 10.0% (w/v) or about 0.01% (w/v) toabout 90.0% (w/v), about 0.01% (w/v) to about 80.0% (w/v), about 0.01%(w/v) to about 70.0% (w/v), about 0.01% (w/v) to about 60.0% (w/v),about 0.01% (w/v) to about 50.0% (w/v), about 0.01% (w/v) to about 40.0%(w/v), about 0.01% (w/v) to about 30.0% (w/v)about 0.01% (w/v) to about20.0% (w/v) or about 0.01% (w/v) to about 10.0% (w/v).

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may be made into aliquid formulation. In an embodiment, liquid formulations suitable forenteral or parenteral administration include, without limitation,solutions, syrups, elixirs, dispersions, emulsions, and suspensions. Inan embodiment, a therapeutic compound or composition disclosed hereinintended for such administration may be prepared, without limitation,according to any method known to the art for the manufacture ofpharmaceutical compositions. In an embodiment, in such liquid dosageforms, a therapeutic compound or composition disclosed herein may beadmixed with, without limitation, (a) suitable aqueous and nonaqueouscarriers, (b) diluents, (c) solvents, such as, without limitation,water, ethanol, propylene glycol, polyethyleneglycol, glycerol,vegetable oils, such as, without limitation, rapeseed oil and olive oil,and injectable organic esters such as ethyl oleate; and/or fluidityagents, such as, without limitation, surfactants or coating agents likelecithin. In the case of dispersions and suspensions, fluidity can alsobe controlled by maintaining a particular particle size. In anembodiment, in liquid formulations, a therapeutically effective amountof a therapeutic compound disclosed herein typically may be betweenabout 0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) to about 80%(w/v), 0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) to about 60%(w/v), 0.0001% (w/v) to about 50% (w/v), 0.0001% (w/v) to about 40%(w/v), 0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) to about 20%(w/v), 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) to about90.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) to about70.0% (w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% (w/v) to about0.0% (w/v), 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) to about30.0% (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) to about10.0% (w/v) or about 0.01% (w/v) to about 90.0% (w/v), about 0.01% (w/v)to about 80.0% (w/v), about 0.01% (w/v) to about 70.0% (w/v), about0.01% (w/v) to about 60.0% (w/v), about 0.01% (w/v) to about 50.0%(w/v), about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) toabout 30.0% (w/v)about 0.01% (w/v) to about 20.0% (w/v) or about 0.01%(w/v) to about 10.0% (w/v).

In an embodiment, syrups and elixirs may be formulated, withoutlimitation, sweetening agents, for example glycerol, propylene glycol,sorbitol or sucrose. In an additional embodiment, such formulations mayalso contain, without limitation, a demulcent, a preservative, flavoringagents, and coloring agents.

In an embodiment, liquid suspensions may be formulated, withoutlimitation, by suspending a therapeutic compound disclosed herein inadmixture with excipients suitable for the manufacture of aqueoussuspensions. In an embodiment, such excipients are suspending agents,for example, without limitation, sodium carboxymethylcellulose,methylcellulose, hydroxypropylmethylcellulose, sodium alginate, pectin,polyvinyl pyrrolidone, polyvinyl alcohol, natural gum, agar, gumtragacanth and gum acacia; dispersing or wetting agents may be anaturally occurring phosphatide, for example lecithin, or condensationproducts of an alkylene oxide with fatty acids, for example, withoutlimitation, polyoxyethylene stearate, or condensation products ofethylene oxide with long-chain aliphatic alcohols, for example, withoutlimitation, heptadecaethyleneoxycetanol, or condensation products ofethylene oxide with partial esters derived from fatty acids, forexample, without limitation, polyoxyethylene sorbitan monooleate.

In an embodiment, oily suspensions may be formulated by suspending atherapeutic compound disclosed herein in admixture with (a) vegetableoils, such as, without limitation, almond oil, arachis oil, avocado oil,canola oil, castor oil, coconut oil, corn oil, cottonseed oil, grapeseed oil, hazelnut oil, hemp oil, linseed oil, olive oil, palm oil,peanut oil, rapeseed oil, rice bran oil, safflower oil, sesame oil,soybean oil, soya oil, sunflower oil, walnut oil, wheat germ oil, or acombination thereof, (b) a saturated fatty acid, an unsaturated fattyacid, or a combination thereof, such as, without limitation, palmiticacid, stearic acid, oleic acid, linoleic acid, linolenic acid, or acombination thereof, (c) mineral oil such as, without limitation, liquidparaffin, (d) surfactants or detergents. In an embodiment, the oilysuspensions may contain a thickening agent, for example beeswax, hardparaffin or cetyl alcohol. In an embodiment, sweetening agents, such asthose set forth above, and flavoring agents may be added to provide apalatable oral preparation. In an embodiment, these compositions may bepreserved by the addition of an antioxidant such as ascorbic acid.

In an embodiment, dispersible powders and granules suitable forpreparation of an aqueous suspension by the addition of water providethe combined therapeutic compounds in admixture with a dispersing orwetting agent, suspending agent and one or more preservatives.

In an embodiment, a therapeutic compound disclosed herein may be in theform of oil-in-water emulsions. In an embodiment, the oily phase may bea vegetable oil as disclosed herein or a mineral oil as disclosed hereinor mixtures thereof. In an additional embodiment, suitable emulsifyingagents may be naturally occurring gums, such as, without limitation, gumacacia or gum tragacanth, naturally occurring phosphatides, for examplesoya bean, lecithin, and esters or partial esters derived from fattyacids and hexitol anhydrides, for example, without limitation, sorbitanmonooleate and condensation products of the said partial esters withethylene oxide, for example polyoxyethylene sorbitan monooleate.

In an embodiment, a therapeutic compound disclosed herein, or acomposition comprising such a therapeutic compound, may also beincorporated into a drug delivery platform in order to achieve acontrolled release profile over time. In an embodiment, such a drugdelivery platform comprises a therapeutic compound disclosed hereindispersed within a polymer matrix, typically, without limitation, abiodegradable, bioerodible, and/or bioresorbable polymer matrix. In anembodiment, as used herein, the term “polymer” refers to synthetic homo-or copolymers, naturally occurring homo- or copolymers, as well as,without limitation, synthetic modifications or derivatives thereofhaving a linear, branched or star structure. In an embodiment,copolymers can be arranged in any form, such as, without limitation,random, block, segmented, tapered blocks, graft, or triblock. In anembodiment, polymers are generally condensation polymers. In anembodiment, polymers can be further modified to enhance their mechanicalor degradation properties by introducing cross-linking agents orchanging the hydrophobicity of the side residues. In an embodiment, ifcrosslinked, polymers are usually less than 75% crosslinked, 65%crosslinked, 55% crosslinked, 45% crosslinked, 35% crosslinked, 25%crosslinked, 15% crosslinked 5% crosslinked, usually less than 1%crosslinked.

In an embodiment, suitable polymers include, without limitation,alginates, aliphatic polyesters, polyalkylene oxalates, polyamides,polyamidoesters, polyanhydrides, polycarbonates, polyesters,polyethylene glycol, polyhydroxyaliphatic carboxylic acids,polyorthoesters, polyoxaesters, polypeptides, polyphosphazenes,polysaccharides, and polyurethanes. In an embodiment, the polymerusually comprises at least about 10% (w/w), at least about 20% (w/w), atleast about 30% (w/w), at least about 40% (w/w), at least about 50%(w/w), at least about 60% (w/w), at least about 70% (w/w), at leastabout 80% (w/w), or at least about 90% (w/w) of the drug deliveryplatform. In an embodiment, examples of biodegradable, bioerodible,and/or bioresorbable polymers and methods useful to make a drug deliveryplatform are described in, e.g., Drost, without limitation, ControlledRelease Formulation, U.S. Pat. No. 4,756,911; Smith, et. al., SustainedRelease Drug Delivery Devices, U.S. Pat. No. 5,378,475; Wong andKochinke, Formulation for Controlled Release of Drugs by CombiningHyrophilic and Hydrophobic Agents, U.S. Pat. No. 7,048,946; Hughes, et.al., Compositions and Methods for Localized Therapy of the Eye, U.S.Patent Publication 2005/0181017; Hughes, Hypotensive Lipid-ContainingBiodegradable Intraocular Implants and Related Methods, U.S. PatentPublication 2005/0244464; Altman, et al., Silk Fibroin Hydrogels andUses Thereof, U.S. Patent Publication 2011/0008437; each of which isincorporated by reference in its entirety.

In an embodiment, a polymer composing the matrix is a polypeptide suchas, without limitation, silk fibroin, keratin, or collagen. In anadditional embodiment, a polymer composing the matrix is apolysaccharide such as, without limitation, cellulose, agarose, elastin,chitosan, chitin, or a glycosaminoglycan like chondroitin sulfate,dermatan sulfate, keratan sulfate, or hyaluronic acid. In yet anotherembodiment, a polymer composing the matrix is a polyester such as,without limitation, D-lactic acid, L-lactic acid, racemic lactic acid,glycolic acid, caprolactone, and combinations thereof.

One of ordinary skill in the art appreciates that the selection of asuitable polymer for forming a suitable disclosed drug delivery platformdepends on several factors. The more relevant factors in the selectionof the appropriate polymer(s), include, without limitation,compatibility of polymer with drug, desired release kinetics of drug,desired biodegradation kinetics of platform at implantation site,desired bioerodible kinetics of platform at implantation site, desiredbioresorbable kinetics of platform at implantation site, in vivomechanical performance of platform, processing temperatures,biocompatibility of platform, and patient tolerance. Other relevantfactors that, to some extent, without limitation, dictate the in vitroand in vivo behavior of the polymer include the chemical composition,spatial distribution of the constituents, the molecular weight of thepolymer and the degree of crystallinity.

In an embodiment, a drug delivery platform includes both a sustainedrelease drug delivery platform and an extended release drug deliveryplatform. In an embodiment, the term “sustained release” refers to therelease of a therapeutic compound or compounds disclosed herein over aperiod of about seven days or more. In an embodiment, the term “extendedrelease” refers to the release of a therapeutic compound or compoundsdisclosed herein over a period of time of less than about seven days.

In an embodiment, a sustained release drug delivery platform releases atherapeutic compound or compounds disclosed herein with substantiallyzero order release kinetics over a period of, without limitation, about3 days after administration, about 7 days after administration, about 10days after administration, about 15 days after administration, about 20days after administration, about 25 days after administration, about 30days after administration, about 45 days after administration, about 60days after administration, about 75 days after administration, or about90 days after administration. In another embodiment, a sustained releasedrug delivery platform releases a therapeutic compound disclosed hereinwith substantially zero order release kinetics over a period , withoutlimitation, at least 3 days after administration, at least 7 days afteradministration, at least 10 days after administration, at least 15 daysafter administration, at least 20 days after administration, at least 25days after administration, at least 30 days after administration, atleast 45 days after administration, at least 60 days afteradministration, at least 75 days after administration, or at least 90days after administration.

In an embodiment, an ADHD therapeutic compound and/or appetite stimulanttherapeutic compound or compounds is in the form of a long actingcomposition that includes, without limitation, extended releasecompositions. An embodiment includes, without limitation, an extendedrelease capsule, tablet or other solid or a liquid formulation thatprovides the therapeutic compound or compounds to the patient to whom itis administered over time. The long acting composition can provideactivity of an ADHD therapeutic compound and/or appetite stimulanttherapeutic compound in a patient administered either or boththerapeutic compounds for 4 hours, 6 hours, 8 hours, 10 hours, 12 hours,16 hours, 20 hours, 24 hours, 28 hours, 30 hours, 32 hours, 34 hours, 36hours, 40 hours, 48 hours, 3 days, 4 days, 5 days, 6 days, 7 days, 2weeks, 3 weeks or 4 weeks. The long acting composition can provideactivity of an ADHD therapeutic compound and/or appetite stimulanttherapeutic compound or compounds in a patient administered either orboth therapeutic compounds for as little as 4 hours or as long as 4weeks, for as little as 4 hours or as long as 3 weeks, for as little as4 hours or as long as 2 weeks, for as little as 4 hours or as long as 1week, for as little as 4 hours or as long as 6 days, for as little as 4hours or as long as 5 days, for as little as 4 hours or as long as 4days, for as little as 4 hours or as long as 3 days, for as little as 4hours or as long as 2 days, for as little as 4 hours or as long as 1day, for as little as 4 hours or as long as 20 hours, for as little as 4hours or as long as 16 hours, for as little as 4 hours or as long as 14hours, for as little as 4 hours or as long as 12 hours, for as little as4 hours or as long as 10 hours, for as little as 4 hours or as long as 8hours, for as little as 4 hours or as long as 6 hours.

In an embodiment, a sustained release drug delivery platform releases atherapeutic compound or compounds disclosed herein with substantiallyfirst order release kinetics over a period of, without limitation, about3 days after administration, about 7 days after administration, about 10days after administration, about 15 days after administration, about 20days after administration, about 25 days after administration, about 30days after administration, about 45 days after administration, about 60days after administration, about 75 days after administration, or about90 days after administration. In other aspects of this embodiment, asustained release drug delivery platform releases a therapeutic compoundor compounds disclosed herein with substantially first order releasekinetics over a period of, without limitation, at least 3 days afteradministration, at least 7 days after administration, at least 10 daysafter administration, at least 15 days after administration, at least 20days after administration, at least 25 days after administration, atleast 30 days after administration, at least 45 days afteradministration, at least 60 days after administration, at least 75 daysafter administration, or at least 90 days after administration.

In an embodiment, a drug delivery platform releases a therapeuticcompound or compounds disclosed herein with substantially zero orderrelease kinetics over a period of, without limitation, about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, about 6 days after administration or about 7 days ormore after administration. In an additional embodiment, a drug deliveryplatform releases a therapeutic compound or compounds disclosed hereinwith substantially zero order release kinetics over a period of, withoutlimitation, at most 1 day after administration, at most 2 days afteradministration, at most 3 days after administration, at most 4 daysafter administration, at most 5 days after administration, at most 6days after administration or at most 7 days or more afteradministration.

In an embodiment, a drug delivery platform releases a therapeuticcompound or compounds disclosed herein with substantially first orderrelease kinetics over a period of, without limitation, about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, about 6 days after administration or about 7 days ormore after administration. In an additional embodiment, a drug deliveryplatform releases a therapeutic compound or compounds disclosed hereinwith substantially first order release kinetics over a period of, e.g.,at most 1 day after administration, at most 2 days after administration,at most 3 days after administration, at most 4 days afteradministration, at most 5 days after administration, at most 6 daysafter administration or at most 7 days or more after administration.

In an embodiment of the present specification disclose, in part,treating an individual suffering from ADHD. As used herein, the term“treating,” refers to reducing or eliminating in an individual aclinical symptom, set of symptoms, or clinical index for ADHD; ordelaying or preventing in an individual the onset of ADHD. In anembodiment, for example , without limitation, the term “treating” canmean reducing a symptom of a condition characterized by ADHD by, withoutlimitation, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% at least 95%, or at least 100%. In an embodiment, the actualsymptoms associated with ADHD are well known and can be determined by aperson of ordinary skill in the art by taking into account factors wellknown, including, without limitation, missing details, forgettingthings, frequently switch from one activity to another, havingdifficulty focusing, organizing, or completing tasks, losing interestafter only a few minutes unless they are doing something they enjoy,having trouble with homework assignments, losing things (eg, pencils,toys, assignments), seeming to not listen when spoken to, daydreaming,become easily confused, and moving slowly. having difficulty processinginformation as quickly and accurately as others do, struggling to followinstructions, fidgeting and squirming in their seats, talking nonstop,running around, touching or playing with anything and everything insight, having trouble sitting still during, without limitation, meals,school, storytime, struggling to do quiet tasks or activities, beingvery patient, blurting out inappropriate comments, showing emotionwithout restraint, acting without regard for consequences and/orinterrupting conversations or other activities. In an embodiment, theactual symptoms associated with ADHD are well known and can bedetermined by a person of ordinary skill in the art by taking intoaccount factors well known, including, without limitation, often doesnot give close attention to details or makes careless mistakes in workor other activities, often has trouble keeping attention on tasks orplay activities, often does not seem to listen when spoken to directly,often does not follow instructions and fails to finish duties in theworkplace, often has trouble organizing activities, often avoids,dislikes, or does not want to do things that take a lot of mental effortfor a long period of time, often loses things needed for tasks andactivities, is often easily distracted, is often forgetful in dailyactivities, often fidgets or squirms in seat, often gets up from seatwhen remaining seated is expected, often feels very restless, often hastrouble enjoying leisure activities quietly, is often on the go or oftenacts as if driven by a motor, often talks impulsively, often blurts outanswers before questions have been finished, often has trouble waitingone's turn and/or often interrupts or intrudes on others.

In an embodiment, the present specification disclose, in part, treatingan individual suffering from appetite reduction. In an embodiment, theterm “treating,” refers to reducing or eliminating in an individual aclinical symptom for appetite reduction; or delaying or preventing in anindividual the onset of appetite reduction. In an embodiment, forexample, without limitation, the term “treating” can mean reducing asymptom of a condition characterized by appetite reduction by, withoutlimitation, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% at least 95%, or at least 100%. In an embodiment, the actualsymptoms associated with appetite reduction are well known and can bedetermined by a person of ordinary skill in the art by taking intoaccount factors well known, including without limitation, failure to eata meal, failure to eat a snack, or failure to eat food.

In an embodiment, the present specification disclose, in part, treatingan individual suffering from weight loss resultant from appetitereduction. In an embodiment, for example, without limitation, anincrease in weight following treatment with an appetite stimulant is by,without limitation, at least 20%, at least 25%, at least 30%, at least35%, at least 40%, at least 45%, at least 50%, at least 55%, at least60%, at least 65%, at least 70%, at least 75%, at least 80%, at least85%, at least 90% at least 95%, or at least 100%. In an embodiment, thepresent specification disclose, in part, treating an individualsuffering from a reduction in height resultant from appetite reduction.In an embodiment, for example, without limitation, an increase in heightfollowing treatment with an appetite stimulant is by, withoutlimitation, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% at least 95%, or at least 100%.

In an embodiment, the present specification disclose, in part, treatingan individual suffering from reduced attentiveness. In an embodiment, asused herein, the term “treating,” refers to reducing or eliminating inan individual a clinical symptom for reduced attentiveness; or delayingor preventing in an individual the onset of reduced attentiveness. In anembodiment, for example, without limitation, the term “treating” canmean reducing a symptom of a condition characterized by reducedattentiveness by, e.g., at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% at least 95%, or at least 100%. The actualsymptoms associated with reduced attentiveness are well known and can bedetermined by a person of ordinary skill in the art by taking intoaccount factors well known, including, without limitation, lack ofmental cognition, lack of ability to interact socially.

In an embodiment, a pharmaceutical composition disclosed herein maycomprise a therapeutic compound in a therapeutically effective amount.In an embodiment, as used herein, without limitation, the term“effective amount” is synonymous with “therapeutically effectiveamount”, “effective dose”, or “therapeutically effective dose.” In anembodiment, the effectiveness of a therapeutic compound disclosed hereinto treat ADHD, treat appetite reduction and/or treat a reduction inattentiveness can be determined, without limitation, by observing animprovement in an individual based upon one or more clinical symptoms,and/or physiological indicators associated with the ADHD, appetitereduction and/or reduction in attentiveness. In an embodiment, animprovement in the symptoms associated with ADHD, appetite reductionand/or reduced attentiveness can be indicated by a reduced need for aconcurrent therapy.

In an embodiment, the appropriate effective amount of a therapeuticcompound disclosed herein to be administered to an individual for thetreatment of ADHD and appetite reduction can be determined by a personof ordinary skill in the art by taking into account factors that arewell known. In an additional embodiment, where repeated administrationof a therapeutic compound is used, an effective amount of a therapeuticcompound will further depend upon factors, including, withoutlimitation, the frequency of administration, the half-life of thetherapeutic compound, or any combination thereof. In an embodiment, itis known by a person of ordinary skill in the art that an effectiveamount of a therapeutic compound disclosed herein can be extrapolatedfrom in vitro assays and in vivo administration studies using animalmodels prior to administration to humans.

Wide variations in the necessary effective amount are to be expected inview of the differing efficiencies of the various routes ofadministration. For instance, without limitation, oral administration ofa therapeutic compound disclosed herein generally would be expected torequire higher dosage levels than administration by inhalation.Similarly, without limitation, systemic administration of a therapeuticcompound disclosed herein would be expected to require higher dosagelevels than a local administration. Variations in these dosage levels,without limitation, can be adjusted using standard empirical routines ofoptimization, which are well-known to a person of ordinary skill in theart. The precise therapeutically effective dosage levels and patternsare preferably determined, without limitation, by the attendingphysician in consideration of the above-identified factors. One skilledin the art will recognize that the condition of the individual can bemonitored, without limitation, throughout the course of therapy and thatthe effective amount of a therapeutic compound disclosed herein that isadministered can be adjusted accordingly.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein reduces a symptom associated with ADHD and/ora psychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, by, without limitation, at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, at least 95% or at least 100%. In an additional embodiment, atherapeutically effective amount of a therapeutic compound disclosedherein reduces a symptom associated with ADHD and/or a psychologicaland/or neurological disorder, including without limitation, migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and tic, by,without limitation, at most 10%, at most 15%, at most 20%, at most 25%,at most 30%, at most 35%, at most 40%, at most 45%, at most 50%, at most55%, at most 60%, at most 65%, at most 70%, at most 75%, at most 80%, atmost 85%, at most 90%, at most 95% or at most 100%. In a furtherembodiment, a therapeutically effective amount of a therapeutic compounddisclosed herein reduces a symptom associated with a ADHD and/or apsychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, by, without limitation, about 10% to about 100%,about 10% to about 90%, about 10% to about 80%, about 10% to about 70%,about 10% to about 60%, about 10% to about 50%, about 10% to about 40%,about 20% to about 100%, about 20% to about 90%, about 20% to about 80%,about 20% to about 20%, about 20% to about 60%, about 20% to about 50%,about 20% to about 40%, about 30% to about 100%, about 30% to about 90%,about 30% to about 80%, about 30% to about 70%, about 30% to about 60%,or about 30% to about 50%.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein reduces a symptom associated with appetitereduction by, without limitation, at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least95% or at least 100%. In an additional embodiment, a therapeuticallyeffective amount of a therapeutic compound disclosed herein reduces asymptom associated with appetite reduction by, without limitation, atmost 10%, at most 15%, at most 20%, at most 25%, at most 30%, at most35%, at most 40%, at most 45%, at most 50%, at most 55%, at most 60%, atmost 65%, at most 70%, at most 75%, at most 80%, at most 85%, at most90%, at most 95% or at most 100%. In a further embodiment, atherapeutically effective amount of a therapeutic compound disclosedherein reduces a symptom associated with a appetite reduction by,without limitation, about 10% to about 100%, about 10% to about 90%,about 10% to about 80%, about 10% to about 70%, about 10% to about 60%,about 10% to about 50%, about 10% to about 40%, about 20% to about 100%,about 20% to about 90%, about 20% to about 80%, about 20% to about 20%,about 20% to about 60%, about 20% to about 50%, about 20% to about 40%,about 30% to about 100%, about 30% to about 90%, about 30% to about 80%,about 30% to about 70%, about 30% to about 60%, or about 30% to about50%.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein reduces a symptom associated with loss ofattentiveness by, without limitation, at least 10%, at least 15%, atleast 20%, at least 25%, at least 30%, at least 35%, at least 40%, atleast 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95% or at least 100%. In other aspects of this embodiment, atherapeutically effective amount of a therapeutic compound disclosedherein reduces a symptom associated with loss of attentiveness by, e.g.,at most 10%, at most 15%, at most 20%, at most 25%, at most 30%, at most35%, at most 40%, at most 45%, at most 50%, at most 55%, at most 60%, atmost 65%, at most 70%, at most 75%, at most 80%, at most 85%, at most90%, at most 95% or at most 100%. In an additional embodiment, atherapeutically effective amount of a therapeutic compound disclosedherein reduces a symptom associated with a loss of attentiveness by,without limitation, about 10% to about 100%, about 10% to about 90%,about 10% to about 80%, about 10% to about 70%, about 10% to about 60%,about 10% to about 50%, about 10% to about 40%, about 20% to about 100%,about 20% to about 90%, about 20% to about 80%, about 20% to about 20%,about 20% to about 60%, about 20% to about 50%, about 20% to about 40%,about 30% to about 100%, about 30% to about 90%, about 30% to about 80%,about 30% to about 70%, about 30% to about 60%, or about 30% to about50%.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein increases the weight or height of anindividual is determined by an increase in the individual's weight orheight velocity as compared to an individual nor receiving a therapeuticcompound for appetite reduction. In an embodiment, weight and/or heightvelocity can be calculated by taking measurements of height and/orweight of an individual over a period of time and measuring an increaseor decrease in an individual's height and/or weight over the period oftime. In an embodiment, weight velocity is calculated by taking threetime points, time 0 upon initiation of medication to treat ADHD, time 1addition of an appetite stimulant, time 2 the last data point afterinitiation of combination treatment. In an embodiment, a formula tocalculate weight and height velocity for stimulant alone is(weightT1−weight T0)/days from Time 0 to time 1. In an embodiment, aformula to calculate weight velocity for combination treatment is(weightT2−weight T1)/days from time 1 to time 2. In an embodiment, toevaluate whether weight velocity increased after addition of an appetitestimulant, the weight velocity of time 0 to time 1 is compared to theweight velocity from time 1 to time 2. In an embodiment, height velocityis calculated by taking three time points, time 0 upon initiation ofmedication to treat ADHD, time 1 addition of an appetite stimulant, time2 the last data point after initiation of combination treatment. Theformula to calculate height velocity for stimulant alone is(weightT1−weight T0)/days from Time 0 to time 1. The formula tocalculate height velocity for combination treatment is (weightT2−weightT1)/days from time 1 to time 2. In an embodiment, to evaluate whetherheight velocity increased after addition of an appetite stimulant, theheight velocity of time 0 to time 1 is compared to the height velocityfrom time 1 to time 2.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein generally is in the range of about 0. 001mg/kg/day to about 100 mg/kg/day. In an additional embodiment, aneffective amount of a therapeutic compound disclosed herein may be,without limitation, at least 0.001 mg/kg/day, at least 0.01 mg/kg/day,at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day,at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, atleast 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, atleast 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day. Ina further embodiment, an effective amount of a therapeutic compounddisclosed herein may be in the range of, without limitation, about 0.001mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to about 15mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, about 0.001mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day to about 30mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100mg/kg/day. In a further embodiment, an effective amount of a therapeuticcompound disclosed herein may be in the range of, without limitation,about 0.01 mg/kg/day to about 10 mg/kg/day, about 0.01 mg/kg/day toabout 15 mg/kg/day, about 0.01 mg/kg/day to about 20 mg/kg/day, about0.01 mg/kg/day to about 25 mg/kg/day, about 0.01 mg/kg/day to about 30mg/kg/day, about 0.01 mg/kg/day to about 35 mg/kg/day, about 0.01mg/kg/day to about 40 mg/kg/day, about 0.01 mg/kg/day to about 45mg/kg/day, about 0.01 mg/kg/day to about 50 mg/kg/day, about 0.01mg/kg/day to about 75 mg/kg/day, or about 0.01 mg/kg/day to about 100mg/kg/day. In a further embodiment, an effective amount of a therapeuticcompound disclosed herein may be in the range of, without limitation,about 0.1 mg/kg/day to about 10 mg/kg/day, about 0.1 mg/kg/day to about15 mg/kg/day, about 0.1 mg/kg/day to about 20 mg/kg/day, about 0.1mg/kg/day to about 25 mg/kg/day, about 0.1 mg/kg/day to about 30mg/kg/day, about 0.1 mg/kg/day to about 35 mg/kg/day, about 0.1mg/kg/day to about 40 mg/kg/day, about 0.1 mg/kg/day to about 45mg/kg/day, about 0.1 mg/kg/day to about 50 mg/kg/day, about 0.1mg/kg/day to about 75 mg/kg/day, or about 0.1 mg/kg/day to about 100mg/kg/day.

In an embodiment, an effective amount of a therapeutic compounddisclosed herein may be in the range of, without limitation, about 1mg/kg/day to about 10 mg/kg/day, about 1 mg/kg/day to about 15mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/day, about 1 mg/kg/day toabout 25 mg/kg/day, about 1 mg/kg/day to about 30 mg/kg/day, about 1mg/kg/day to about 35 mg/kg/day, about 1 mg/kg/day to about 40mg/kg/day, about 1 mg/kg/day to about 45 mg/kg/day, about 1 mg/kg/day toabout 50 mg/kg/day, about 1 mg/kg/day to about 75 mg/kg/day, or about 1mg/kg/day to about 100 mg/kg/day. In an additional embodiment, aneffective amount of a therapeutic compound disclosed herein may be inthe range of, without limitation, about 5 mg/kg/day to about 10mg/kg/day, about 5 mg/kg/day to about 15 mg/kg/day, about 5 mg/kg/day toabout 20 mg/kg/day, about 5 mg/kg/day to about 25 mg/kg/day, about 5mg/kg/day to about 30 mg/kg/day, about 5 mg/kg/day to about 35mg/kg/day, about 5 mg/kg/day to about 40 mg/kg/day, about 5 mg/kg/day toabout 45 mg/kg/day, about 5 mg/kg/day to about 50 mg/kg/day, about 5mg/kg/day to about 75 mg/kg/day, or about 5 mg/kg/day to about 100mg/kg/day.

In an embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein generally is in the range of about 1 mg/day toabout 3,000 mg/day. In an additional embodiment, an effective amount ofa therapeutic compound disclosed herein may be, without limitation, atleast 50 mg/day, at least 100 mg/day, at least 150 mg/day, at least 200mg/day, at least 250 mg/day, at least 300 mg/day, at least 350 mg/day,at least 400 mg/day, at least 450 mg/day, at least 500 mg/day, at least550 mg/day, at least 600 mg/day, at least 650 mg/day, at least 700mg/day, at least 750 mg/day, at least 800 mg/day, at least 850 mg/day,at least 900 mg/day, at least 950 mg/day, at least 1,000 mg/day, atleast 1,50 mg/day, at least 1,100 mg/day, at least 1,150 mg/day, atleast 1,200 mg/day, at least 1,250 mg/day, at least 1,300 mg/day, atleast 1,350 mg/day, at least 1,400 mg/day, at least 1,450 mg/day, atleast 1,500 mg/day, at least 1,600 mg/day, at least 1,700 mg/day, atleast 1,800 mg/day, at least 1,900 mg/day, at least 2,000 mg/day, atleast 2,100 mg/day, at least 2,200 mg/day, at least 2,300 mg/day, atleast 2,400 mg/day, at least 2,500 mg/day, at least 2,600 mg/day, atleast 2,700 mg/day, at least 2,800 mg/day, at least 2,900 mg/day, or atleast 3,000 mg/day. In an additional embodiment, an effective amount ofa therapeutic compound disclosed herein may be between, withoutlimitation, about 50 mg/day to about 1,000 mg/day, about 100 mg/day toabout 1,000 mg/day, about 150 mg/day to about 1,000 mg/day, about 200mg/day to about 1,000 mg/day, about 250 mg/day to about 1,000 mg/day,about 300 mg/day to about 1,000 mg/day, about 350 mg/day to about 1,000mg/day, about 400 mg/day to about 1,000 mg/day, about 450 mg/day toabout 1,000 mg/day, about 500 mg/day to about 1,000 mg/day, about 50mg/day to about 1,500 mg/day, about 100 mg/day to about 1,500 mg/day,about 150 mg/day to about 1,500 mg/day, about 200 mg/day to about 1,500mg/day, about 250 mg/day to about 1,500 mg/day, about 300 mg/day toabout 1,500 mg/day, about 350 mg/day to about 1,500 mg/day, about 400mg/day to about 1,500 mg/day, about 450 mg/day to about 1,500 mg/day,about 500 mg/day to about 1,500 mg/day, about 1,000 mg/day to about3,000 mg/day, about 1,100 mg/day to about 3,000 mg/day, about 1,200mg/day to about 3,000 mg/day, about 1,3000 mg/day to about 3,000 mg/day,about 1,400 mg/day to about 3,000 mg/day, about 1,500 mg/day to about3,000 mg/day, about 1,600 mg/day to about 3,000 mg/day, about 1,700mg/day to about 3,000 mg/day, about 1,800 mg/day to about 3,000 mg/day,about 1,900 mg/day to about 3,000 mg/day, or about 2,000 mg/day to about3,000 mg/day.

In an embodiment, a therapeutically effective amount of an amphetamine,methylphenidate or cyproheptadine disclosed herein generally is in therange of about 0. 001 mg/kg/day to about 100 mg/kg/day. In an additionalembodiment, an effective amount of an amphetamine disclosed herein maybe, without limitation, at least 0.001 mg/kg/day, at least 0.01mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50mg/kg/day. In a further embodiment, an effective amount of anamphetamine, methylphenidate or cyproheptadine disclosed herein may bein the range of, without limitation, about 0.001 mg/kg/day to about 10mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day. In a furtherembodiment, an effective amount of an amphetamine, methylphenidate orcyproheptadine disclosed herein may be in the range of, withoutlimitation, about 0.01 mg/kg/day to about 10 mg/kg/day, about 0.01mg/kg/day to about 15 mg/kg/day, about 0.01 mg/kg/day to about 20mg/kg/day, about 0.01 mg/kg/day to about 25 mg/kg/day, about 0.01mg/kg/day to about 30 mg/kg/day, about 0.01 mg/kg/day to about 35mg/kg/day, about 0.01 mg/kg/day to about 40 mg/kg/day, about 0.01mg/kg/day to about 45 mg/kg/day, about 0.01 mg/kg/day to about 50mg/kg/day, about 0.01 mg/kg/day to about 75 mg/kg/day, or about 0.01mg/kg/day to about 100 mg/kg/day. In a further embodiment, an effectiveamount of an amphetamine, methylphenidate or cyproheptadine disclosedherein may be in the range of, without limitation, about 0.1 mg/kg/dayto about 10 mg/kg/day, about 0.1 mg/kg/day to about 15 mg/kg/day, about0.1 mg/kg/day to about 20 mg/kg/day, about 0.1 mg/kg/day to about 25mg/kg/day, about 0.1 mg/kg/day to about 30 mg/kg/day, about 0.1mg/kg/day to about 35 mg/kg/day, about 0.1 mg/kg/day to about 40mg/kg/day, about 0.1 mg/kg/day to about 45 mg/kg/day, about 0.1mg/kg/day to about 50 mg/kg/day, about 0.1 mg/kg/day to about 75mg/kg/day, or about 0.1 mg/kg/day to about 100 mg/kg/day.

In an embodiment, an effective amount of an amphetamine, methylphenidateor cyproheptadine disclosed herein may be in the range of, withoutlimitation, about 1 mg/kg/day to about 10 mg/kg/day, about 1 mg/kg/dayto about 15 mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/day, about 1mg/kg/day to about 25 mg/kg/day, about 1 mg/kg/day to about 30mg/kg/day, about 1 mg/kg/day to about 35 mg/kg/day, about 1 mg/kg/day toabout 40 mg/kg/day, about 1 mg/kg/day to about 45 mg/kg/day, about 1mg/kg/day to about 50 mg/kg/day, about 1 mg/kg/day to about 75mg/kg/day, or about 1 mg/kg/day to about 100 mg/kg/day. In an additionalembodiment, an effective amount of an amphetamine, methylphenidate orcyproheptadine disclosed herein may be in the range of, withoutlimitation, about 5 mg/kg/day to about 10 mg/kg/day, about 5 mg/kg/dayto about 15 mg/kg/day, about 5 mg/kg/day to about 20 mg/kg/day, about 5mg/kg/day to about 25 mg/kg/day, about 5 mg/kg/day to about 30mg/kg/day, about 5 mg/kg/day to about 35 mg/kg/day, about 5 mg/kg/day toabout 40 mg/kg/day, about 5 mg/kg/day to about 45 mg/kg/day, about 5mg/kg/day to about 50 mg/kg/day, about 5 mg/kg/day to about 75mg/kg/day, or about 5 mg/kg/day to about 100 mg/kg/day.

In an embodiment, dosing can be single dosage or cumulative (serialdosing), and can be readily determined by one skilled in the art. In anadditional embodiment, treatment of ADHD and/or a psychological and/orneurological disorder, including without limitation, migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and tic, maycomprise a one-time administration of an effective dose of apharmaceutical composition disclosed herein. In a further embodiment,treatment of ADHD and/or a psychological and/or neurological disorder,including without limitation, migraine, anti-serotonergic side effects,narcolepsy, excessive sleepiness associated with shift work, obstructivesleep apnea as an adjunct to continuous positive airways pressure(“CPAP”), exogenous obesity, disruptive behaviour disorder includingoppositional defiant disorder (“ODD”) and conduct disorder (“CD”),obesity, depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic, may comprise multiple administrations of aneffective dose of a pharmaceutical composition carried out over a rangeof time periods, such as, e.g., once daily, twice daily, trice daily,once every few days, or once weekly. In an embodiment, the timing ofadministration can vary from individual to individual, depending uponsuch factors as the severity of an individual's symptoms. For example,in an embodiment, without limitation, an effective dose of apharmaceutical composition disclosed herein can be administered to anindividual once daily for an indefinite period of time, or until theindividual no longer requires therapy. A person of ordinary skill in theart will recognize that the condition of the individual can be monitoredthroughout the course of treatment and that the effective amount of apharmaceutical composition disclosed herein that is administered can beadjusted accordingly.

In an embodiment, various routes of administration can be useful foradministering a therapeutic compound disclosed herein, according to amethod of treating a coughing condition disclosed herein. In anembodiment, a pharmaceutical composition may be administered to anindividual by any of a variety of means depending, without limitation,on the type of condition to be treated, the location of the condition tobe treated, the specific therapeutic compound or composition used, orother compound to be included in the composition, and the history, riskfactors and symptoms of the individual. As such, without limitation,topical, sublingual, rectal, vaginal, trancutaneious, oral, inhaled,intranasal, subcutaneous, intravenous, enteral or parenteral routes ofadministration may be suitable for of treating ADHD and/or apsychological and/or neurological disorder, including withoutlimitation, migraine, anti-serotonergic side effects, narcolepsy,excessive sleepiness associated with shift work, obstructive sleep apneaas an adjunct to continuous positive airways pressure (“CPAP”),exogenous obesity, disruptive behaviour disorder including oppositionaldefiant disorder (“ODD”) and conduct disorder (“CD”), obesity,depression (including, without limitation, augmentation ofantidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and tic disclosed herein and such routes include, withoutlimitation, both local and systemic delivery of a therapeutic compoundor composition disclosed herein. In an embodiment, compositionscomprising either a single therapeutic compound disclosed herein, or twoor more therapeutic compounds disclosed herein are intended for inhaled,enteral, parenteral, topical, intranasal, sublingual, subcutaneous,intravenous, rectal, transcutaneous (for example, without limitation,through a patch placed on the skin of an individual being treated)and/or vaginal use may be prepared according to any method known to theart for the manufacture of pharmaceutical compositions.

In an embodiment, the therapeutic compound includes, without limitation,an extended release, sustained release or long acting form. In anadditional embodiment, the extended release, sustained release or longacting form of a therapeutic compound is linked, without limitation, toa polymer, including, without limitation, to a water soluble polymer. Inan embodiment, a water-soluble polymer is selected, without limitation,from the group consisting of poly(alkylene oxide), poly(vinylpyrrolidone), poly(vinyl alcohol), polyoxazoline,poly(acryloylmorpholine), and combinations thereof. In an additionalembodiment, the water soluble polymer is a poly(alkylene oxide) such as,without limitation, a poly(ethylene glycol) derivative. In anembodiment, a water soluble polymer has, without limitation, a nominalaverage molecular weight in the range from about 2,000 Daltons to about150,000 Daltons, from about 2,000 Daltons to about 125,000 Daltons, fromabout 2,000 Daltons to about 100,000 Daltons, from about 2,000 Daltonsto about 75,000 Daltons, from about 2,000 Daltons to about 50,000Daltons, from about 2,000 Daltons to about 25,000 Daltons, from about5,000 Daltons to about 150,000 Daltons, from about 5,000 Daltons toabout 100,000 Daltons, from about 5,000 Daltons to about 75,000 Daltons,from about 5,000 Daltons to about 50,000 Daltons, from about 5,000Daltons to about 25,000 Daltons, from about 10,000 Daltons to about100,000 Daltons, from about 10,000 Daltons to about 75,000 Daltons, fromabout 10,000 Daltons to about 50,000 Daltons, from about 10.,000 Daltonsto about 25,000 Daltons. In an embodiment, a water soluble polymer has,without limitation, a nominal average molecular weight of at least150,000 Daltons, at least 125,000 Daltons, at least 100,000 Daltons, atleast 75,000 Daltons, at least 50,000 Daltons, at least 25,000 Daltons.In an additional embodiment, the extended release, sustained release orlong acting form of a therapeutic compound is linked, withoutlimitation, to a polymer, including, without limitation, to a watersoluble polymer through, without limitation, a stable linker or areleasable linker.

In an embodiment, the pharmaceutical compositions of the invention,including, without limitation a therapeutic compound, may furthercomprise one or more pharmaceutically acceptable excipients to provide apharmaceutical composition. In an additional embodiment, excipientsinclude, without limitation, carbohydrates, starches (e.g., cornstarch), inorganic salts, antimicrobial agents, antioxidants,binders/fillers, surfactants, lubricants (e.g., calcium or magnesiumstearate), glidants such as talc, disintegrants, diluents, buffers,acids, bases, film coats, combinations thereof, and the like.

In an embodiment, a pharmaceutical composition of the invention,including, without limitation a therapeutic compound, may include one ormore carbohydrates such as a sugar, a derivatized sugar such as analditol, aldonic acid, an esterified sugar, and/or a sugar polymer.Specific carbohydrate excipients include, for example, withoutlimitation: monosaccharides, such as fructose, maltose, galactose,glucose, D-mannose, sorbose, and the like; disaccharides, such aslactose, sucrose, trehalose, cellobiose, and the like; polysaccharides,such as raffinose, melezitose, maltodextrins, dextrans, starches, andthe like; and alditols, such as mannitol, xylitol, maltitol, lactitol,xylitol, sorbitol (glucitol), pyranosyl sorbitol, myoinositol, and thelike.

In an embodiment, pharmaceutical compositions of the invention,including, without limitation, a therapeutic compound, are potato andcorn-based starches such as sodium starch glycolate and directlycompressible modified starch.

In an embodiment, further representative excipients include, withoutlimitation, inorganic salt or buffers such as citric acid, sodiumchloride, potassium chloride, sodium sulfate, potassium nitrate, sodiumphosphate monobasic, sodium phosphate dibasic, and combinations thereof.

In an embodiment, the pharmaceutical composition, including, withoutlimitation, a therapeutic compound, may also include, withoutlimitation, an antimicrobial agent, without limitation, for preventingor deterring microbial growth. In an embodiment, non-limiting examplesof antimicrobial agents suitable for the present invention include,without limitation, benzalkonium chloride, benzethonium chloride, benzylalcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethylalcohol, phenylmercuric nitrate, thimersol, and combinations thereof.

In an embodiment, a pharmaceutical composition of the invention,including, without limitation a therapeutic compound may also containone or more antioxidants. In an additional embodiment, antioxidants areused to prevent oxidation, thereby preventing the deterioration of thedrug(s) or other components of the preparation. In a further embodiment,suitable antioxidants for use in the present invention include, forexample, without limitation, ascorbyl palmitate, butylatedhydroxyanisole, butylated hydroxytoluene, hypophosphorous acid,monothioglycerol, propyl gallate, sodium bisulfite, sodium formaldehydesulfoxylate, sodium metabisulfite, and combinations thereof.

In an embodiment, additional excipients include, without limitation,surfactants such as polysorbates without limitation, “Tween 20” and“Tween 80,” and pluronics such as, without limitation, F68 and F88 (bothof which are available from BASF, Mount Olive, N.J.), sorbitan esters,lipids (e.g., phospholipids such as lecithin and otherphosphatidylcholines, and phosphatidylethanolamines), fatty acids andfatty esters, steroids such as cholesterol, and chelating agents, suchas EDTA, zinc and other such suitable cations.

In an embodiment, a pharmaceutical composition of the invention,including, without limitation a therapeutic compound, may optionallyinclude one or more acids or bases. In an embodiment, non-limitingexamples of acids that can be used include, without limitation, thoseacids selected from the group consisting of hydrochloric acid, aceticacid, phosphoric acid, citric acid, malic acid, lactic acid, formicacid, trichloroacetic acid, nitric acid, perchloric acid, phosphoricacid, sulfuric acid, fumaric acid, and combinations thereof. In anembodiment, suitable bases include, without limitation, bases selectedfrom the group consisting of sodium hydroxide, sodium acetate, ammoniumhydroxide, potassium hydroxide, ammonium acetate, potassium acetate,sodium phosphate, potassium phosphate, sodium citrate, sodium formate,sodium sulfate, potassium sulfate, potassium fumerate, and combinationsthereof.

In an embodiment, the amount of any individual excipient in thecomposition will vary depending on the role of the excipient, the dosagerequirements of the active agent components, and particular needs of thecomposition. In an embodiment, the optimal amount of any individualexcipient is determined through routine experimentation, withoutlimitation, by preparing compositions containing varying amounts of theexcipient (ranging from low to high), examining the stability and otherparameters, and then determining the range at which optimal performanceis attained with no significant adverse effects.

In an embodiment, the excipient will be present in the composition in anamount of, without limitation, about 1% to about 99% by weight,preferably from about 5% to about 98% by weight, more preferably fromabout 15 to about 95% by weight of the excipient, with concentrationsless than 30% by weight most preferred.

These foregoing pharmaceutical excipients along with other excipientsare described in “Remington: The Science & Practice of Pharmacy”,19.sup.th ed., Williams & Williams, (1995), the “Physician's DeskReference”, 52.sup.nd ed., Medical Economics, Montvale, N.J. (1998), andKibbe, A. H., Handbook of Pharmaceutical Excipients, 3.sup.rd Edition,American Pharmaceutical Association, Washington, D.C., 2000.

In an embodiment, the compositions encompass all types of formulationsand in particular those that are suited for oral administration, withoutlimitation, tablets, lozenges, orally dissolved strips, capsules,syrups, oral suspensions, emulsions, granules, sprinkles and pellets. Inan additional embodiment, formulations include, without limitation,aerosols, transdermal patches, gels, creams, ointments, suppositories,powders or lyophilates that can be reconstituted, as well as liquids,such as for use in an oral or parenteral product. In an embodiment,suitable diluents for reconstituting solid compositions, withoutlimitation, prior to injection, include bacteriostatic water forinjection, dextrose 5% in water, phosphate-buffered saline, Ringer'ssolution, saline, sterile water, deionized water, and combinationsthereof. In an additional embodiment, liquid pharmaceuticalcompositions, solutions and suspensions are envisioned.

In an embodiment, for oral, rectal, vaginal, sublingual and/orintranasal delivery formulations, tablets can be made by compression ormolding, optionally with one or more accessory ingredients or additives.In an embodiment, compressed tablets are prepared, for example, bycompressing in a suitable tabletting machine, the active ingredients ina free-flowing form such as a powder or granules, optionally mixed witha binder (for example, without limitation, povidone, gelatin,hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative,disintegrant (for example, without limitation, sodium starch glycolate,cross-linked povidone, cross-linked sodium carboxymethyl cellulose)and/or surface-active or dispersing agent.

In an embodiment, molded tablets are made, for example, withoutlimitation, by molding in a suitable tabletting machine, a mixture ofpowdered compounds moistened with an inert liquid diluent. In anembodiment, the tablets may optionally be coated or scored, and may beformulated so as to provide slow or controlled release of the activeingredients, using, for example, without limitation, hydroxypropylmethylcellulose in varying proportions to provide the desired release profile.In an embodiment, tablets may optionally be provided with a coating,without limitation, such as a thin film, sugar coating, or an entericcoating to provide release in parts of the gut other than the stomach.In an embodiment, processes, equipment, and toll manufacturers fortablet and capsule making are well-known in the art.

In an embodiment, capsule formulations may utilize, without limitation,either hard or soft capsules, including, without limitation, gelatincapsules or vegetarian capsules such as those made out ofhydroxymethylpropylcellulose (HMPC). In an embodiment, a type of capsuleis a gelatin capsule. In an embodiment, capsules may be filled using acapsule filling machine such as, without limitation, those availablefrom commercial suppliers such as Miranda International or employingcapsule manufacturing techniques well-known in the industry, asdescribed in detail in Pharmaceutical Capsules, 2.sup.nd Ed., F.Podczeck and B. Jones, 2004. In an embodiment, capsule formulations maybe prepared, without limitation, using a toll manufacturing center suchas the Chao Center for Industrial Pharmacy & Contract Manufacturing,located at Purdue Research Park.

In an embodiment, formulations for topical administration in the mouthinclude lozenges comprising, without limitation, the active ingredients,generally in a flavored base such as sucrose and acacia or tragacanthand pastilles comprising the active ingredients in an inert base such asgelatin and glycerin or sucrose and acacia.

In an embodiment, a pharmaceutical composition for topicaladministration may also be formulated, without limitation, as anointment, cream, suspension, lotion, powder, solution, paste, gel,spray, aerosol or oil. In an embodiment, the formulation may be, withoutlimitation, in the form of a patch (e.g., a transdermal patch) or adressing such as a bandage or adhesive plaster impregnated with activeingredients and optionally one or more excipients or diluents. In anembodiment, topical formulations may additionally, without limitation,include a compound that enhances absorption or penetration of theingredients through the skin or other affected areas, such asdimethylsulfoxidem bisabolol, oleic acid, isopropyl myristate, andD-limonene, to name a few.

In an embodiment, for emulsions, the oily phase is constituted, withoutlimitation, from known ingredients in a known manner. In an embodiment,while this phase may comprise merely an emulsifier (otherwise known asan emulgent), it desirably comprises, without limitation, a mixture ofat least one emulsifier with a fat and/or an oil. In an embodiment, ahydrophilic emulsifier is included, without limitation, together with alipophilic emulsifier that acts as a stabilizer. In an embodiment, theemulsifier(s) with or without stabilizer(s) make up, without limitation,the so-called emulsifying wax, and the wax together with the oil and/orfat make up, without limitation, the so-called emulsifying ointment basewhich forms the oily dispersed phase of cream formulations. In anembodiment, illustrative emulgents and emulsion stabilizers include,without limitation, Tween 60, Span 80, cetostearyl alcohol, myristylalcohol, glyceryl monostearate and sodium lauryl sulfate.

In an embodiment, formulations for rectal administration are typically,without limitation, in the form of a suppository with a suitable basecomprising, for example, cocoa butter or a salicylate.

In an embodiment, formulations suitable for vaginal administrationgenerally take the form, without limitation, of a suppository, tampon,cream, gel, paste, foam or spray.

In an embodiment, formulations suitable for nasal administration,wherein the carrier is a solid, include, without limitation, a coarsepowder having a particle size, for example, without limitation, in therange of about 20 to about 500 microns. In an additional embodiment,such a formulation is typically administered, without limitation, byrapid inhalation through the nasal passage, for example, withoutlimitation, from a container of the powder held in proximity to thenose. In an embodiment, a formulation for nasal delivery may be, withoutlimitation, in the form of a liquid, e.g., a nasal spray or nasal drops.

In an embodiment, aerosolizable formulations for inhalation may be,without limitation, in dry powder form (e.g., suitable foradministration by a dry powder inhaler), or, alternatively, may be inliquid form, e.g., for use in a nebulizer. In an embodiment, nebulizersfor delivering an aerosolized solution include, without limitation, theAERx™ (Aradigm), the Ultravent® (Mallinkrodt), and the Acorn II®(Marquest Medical Products). In an embodiment, a composition of theinvention may also, without limitation, be delivered using apressurized, metered dose inhaler (MDI), e.g., the Ventolin® metereddose inhaler, containing a solution or suspension of a combination ofdrugs as described herein in a pharmaceutically inert liquid propellant,for example, without limitation, a chlorofluorocarbon or fluorocarbon.

In an embodiment, formulations suitable for parenteral administrationinclude, without limitation, aqueous and non-aqueous isotonic sterilesolutions suitable for injection, as well as aqueous and non-aqueoussterile suspensions.

In an embodiment, parenteral formulations of the invention areoptionally contained, without limitation, in unit-dose or multi-dosesealed containers, for example, without limitation, ampoules and vials,and may be stored in a freeze-dried (lyophilized) condition requiringonly the addition of the sterile liquid carrier, for example, water forinjections, immediately prior to use. In an embodiment, extemporaneousinjection solutions and suspensions may be prepared, without limitation,from sterile powders, granules and tablets of the types previouslydescribed.

In an embodiment, a formulation of the invention may also be, withoutlimitation, a sustained release formulation, such that each of the drugcomponents is released or absorbed slowly over time, when compared to anon-sustained release formulation. In an embodiment, sustained releaseformulations may, without limitation, employ pro-drug forms of theactive agent, delayed-release drug delivery systems such as, withoutlimitation, liposomes or polymer matrices, hydrogels, or covalentattachment of a polymer such as polyethylene glycol to the active agent.

In an embodiment, in addition to the ingredients particularly mentionedabove, the formulations of the invention may optionally include, withoutlimitation, other agents conventional in the pharmaceutical arts andparticular type of formulation being employed, for example, withoutlimitation, for oral administration forms, the composition for oraladministration may also include additional agents as sweeteners,thickeners or flavoring agents.

In an embodiment, the compositions of the present invention may also beprepared, without limitation, in a form suitable for veterinaryapplications.

In an embodiment, the anti-arthritic compositions described herein are,without limitation, in unit dosage form, meaning a quantity of acombination of drugs of the invention, appropriate for a single dose, ormultiple doses, in one or more premeasured or pre-packaged forms. In anadditional embodiment, a type of solid dosage form, without limitation,is a capsule containing each of an antiviral compound, a broad-spectrumantibiotic, and an antiprotozoal compound, or any two of the foregoing.In an embodiment, dosage forms and modes of administration are discussedin greater detail in the sections that follow.

In an embodiment, provided herein is a kit or package containing,without limitation, at least one combination composition of theinvention, accompanied by instructions for use.

In an embodiment, in instances in which each of the drugs themselves areadministered, without limitation, as individual or separate dosage forms(e.g., capsules or tablets), the kit comprises, without limitation, eachof the drugs making up the composition of the invention, along withinstructions for use. In an additional embodiment, the drug components,without limitation, may be packaged in any manner suitable foradministration, so long as the packaging, when considered along with theinstructions for administration, without limitation, clearly indicatesthe manner in which each of the drug components is to be administered.In a further embodiment, each of the drug components of the combinationmay, without limitation, be combined into a single administrable dosageform such as a capsule.

Various embodiments according to the above may be readily envisioned,and would of course depend upon the particular combination of drugsemployed for treatment, their corresponding dosage forms, recommendeddosages, intended patient population, and the like. In an embodiment,the packaging may be in any form commonly employed for the packaging ofpharmaceuticals, such as medication punch cards or blisters, and mayutilize any of a number of features such as different colors, wrapping,tamper-resistant packaging, blister paks, dessicants, and the like.

EXAMPLES Example 1: Treatment of a Patient Suffering From ADHD with andwithout an Appetite Stimulant

A patient suffering from ADHD is prescribed and administered anamphetamine to treat ADHD. The patient takes the amphetamine once a dayin the morning or afternoon. Following administration, the patientsuffers a loss of appetite and reduces their caloric intake. As aresult, the glucose level measured in the blood drops as shown in FIG. 1and the patient suffers a lack of attentiveness as measured by CGI-S andCGI-I. When the patient is administered an amphetamine andCyproheptadine once a day either in the morning or afternoon, thepatient's appetite resumes and the patient increases their caloricintake. As a result, the glucose level measured in the blood increasesas shown in FIG. 1 and the patient's attentiveness recovers as measuredby CGI-S and CGI-I. By taking the appetite stimulant during the timewhen the patient was awake, the patient increased their caloric intakeduring times when the patient needed to maintain their attentiveness inorder to have reasonable cognition and/or social behaviour.

Example 2: Once a Day Periactin

Case study: A six-year and ten month old girl was presented by herparents for symptoms of attention deficit hyperactivity disorder. Hersize at evaluation was 4′ 1¾″ and 50 lbs, corresponding to the 81^(st)and 50^(th) percentiles when compared to girls her age. She respondedwell to treatment with various forms of methylphenidate, utilizing atvarious times both short-acting formulations, as well as a trial on atransdermal patch. A side-effect suffered by the girl was suppression ofappetite and a lack of significant weight gain. At three monthsfollowing the initiation of treatment for ADHD, the girl was 4′ 2⅞″ and50½ lbs, corresponding to the 85^(th) and 34^(rd) percentiles whencompared to girls her age. At one year, she was 4′ 4⅜″ and 53 lbs,corresponding to the 84^(th) and 36^(th) percentiles when compared togirls her age. At two years she was 4′ 5¾″ and 54 lbs, corresponding tothe 72^(nd) and 17^(th) percentiles when compared to girls her age. Atfour years of treatment she was 4′ 7¾″ and 59 lbs, corresponding to70^(th) and 14^(th) percentiles when compared to girls her age. At fiveyears of treatment she was 4′ 9 7/7″ and 64½ lbs, corresponding to59^(th) and 7^(th) percentiles when compared to girls her age.

The girl was then prescribed Periactin at a dosage of 2 mg b.i.d. toattempt to stimulate appetite. The dose was taken in the morning andthen in the afternoon. After one year she was 4′ 11½″ and 72½ lbs,corresponding to 33^(rd) and 5^(th) percentiles when compared to girlsher age. The girl was then prescribed Periactin at a dose of 4 mg b.i.d.After two months on this dose, she was 5′ ¼″ and 76 lbs, correspondingto 37^(th) and 8^(th) percentiles when compared to girls her age. At 8months on this dose, she was 5′½″ and 80 lbs, corresponding to 41^(st)and 8^(th) percentiles when compared to girls her age. At one year onthis dose, she was 5′ 2¾″ and 89½ lbs, corresponding to 51^(st) and17^(th) percentiles when compared to girls her age. At 18 months on thisdose, she was 5′ 3⅝″ and 99½ lbs, corresponding to 56^(th) and 30^(th)percentiles when compared to girls her age. Additionally, theattentiveness of the girl increase following the prescription ofPeriactin as she increased her food intake during the day.

Example 3 Treatment of Patients Suffering From ADHD and Reduction inAppetite

Eight patients, identified as patients A-H, that came in suffering fromADHD were treated for ADHD. Each patient was prescribed an amphetamineor methylphenidate to treat ADHD and each patient following suchtreatment suffered a reduction in appetite and failed to gain sufficientweight. Each patient was then prescribed an appetite simulant to betaken along with the amphetamine or methylphenidate. The patients'weight, height and attentiveness were then followed during the course oftreatment.

The age range of the patients was from 6-15 years of age, with a meanage at the start of treatment for ADHD of 8.4 years of age. The mean ageat the start of the combination treatment wherein the patient wasadministered an amphetamine or methylphenidate and an appetite stimulantwas 10.3 years of age. The mean treatment period for the eight patientswas 1,108 days with a mean of 2.55 ADHD medication changes during thetreatment period. Attentiveness in the eight patients was measured usingCGI-S and CGI-I. Patients weight and height velocity were measured toidentify a difference in weight and height gain prior to and afteraddition of an appetite stimulant to the treatment for ADHD. Weightvelocity was calculated by taking three time points, time 0 uponinitiation of medication to treat ADHD, time 1 addition of an appetitestimulant, time 2 the last data point after initiation of combinationtreatment. The formula to calculate weight velocity for stimulant aloneis (weightT1−weight T0)/days from Time 0 to time 1. The formula tocalculate weight velocity for combination treatment is (weightT2−weightT1)/days from time 1 to time 2.

Following initiation of treatment for ADHD, but prior to the initiationof combination treatment, the mean loss by a patient was 41 percentilepoints in the weight curve as compared to the expected weight gain overthe same time period by the patient if not provided the ADHD treatment.The mean loss was 34 percentile points in the height curve as comparedto the expected growth in height over the same time period by thepatient if not provided the ADHD treatment. For the eight patients, themean weight velocity with the ADHD treatment only was 3.455 g/day. Thiscompares to a mean weight velocity of 13.972 g/day in patientsadministered the combination treatment as shown in FIG. 2. Thiscorresponded to a 304% increase in the weight gain by the patientsfollowing administration of the combination treatment comprising anamphetamine or methylphenidate and an appetite stimulant,Cyproheptadine. Similarly, the eight patients saw an increase in theirheight velocity following initiation of the combination treatment. Themean height velocity of the eight patients when administered only atreatment for ADHD was 0.091 cm/day. This compared to a mean heightvelocity of 0.180 cm/day in patients following administration of thecombination treatment. This corresponds to a 98% increase in the rate ofheight addition for patients following initiation of the combinationtreatment. In addition, the eight patients saw a mean increase of 17.5percentile points in their weight curve following the initiation ofcombination treatment versus the aforementioned loss of 41 percentilepoints for administration of the ADHD treatment without an appetitestimulant. Concordantly, the eight patients saw a mean increase of 16.7percentile points in their height curve following the initiation ofcombination treatment versus the aforementioned loss of 34 percentilepoints for administration of the ADHD treatment without an appetitestimulant.

The mean number of days to the first follow-up with a patient followinginitiation of the combination treatment was 73 days. At this firstfollow-up, the mean weight velocity of the patient was 27.3 g/day. Thisresulted in a 790% increase in weight addition with combinationtreatment at the first follow-up. Further, all eight patients on thecombination treatment were able to maintain their highest weight as ofthe last follow-up date.

Example 4: Patient A

Patient A was a male who was 6 years and approximately 3 months whentreatment for ADHD was initiated. Patient A was administered 18 mg ofConcerts. Initially, following a short loss in weight, patient A beganto gain weight, but at about day 371 after initiation of treatment,Patient A began to lose weight again as shown in FIG. 4. The loss ofweight continued until on day 661 Patient A was prescribed and began totake 4 mg. b.i.d. of Periactin. Following initiation of the combinationtreatment, Patient A began to gain weight and the increase in heightbegan to accelerate as shown in FIG. 4. Additionally, followinginitiation of the combination treatment, Patient A also saw a decreasein his CGI-S score, going from a score of 4 that had been constant foralmost 400 days to a score of 3 as shown in FIG. 5.

Example 5: Patient B

Patient B was a male who was 7 years and approximately 8 months whentreatment for ADHD was initiated. Patient B was administered 10 mg ofFocalin XR at the initiation of treatment for ADHD. The dose of FocalinXR was raised to 15 mg approximately 8 months later. Initially, weightgain was slow and then became slightly erratic with gains of weightbetween follow-up appointments followed by loss of weight as shown inFIG. 6. On day 865 following the initiation of treatment with Focalin XRfor ADHD, Patient B began a combination treatment that included bothFocalin XR at 15 mg and Periactin at 4 mg b.i.d. Following initiation ofcombination therapy, Patient B began to gain weight as shown in FIG. 6,but their CGI-S score remained 3 as shown in FIG. 7. With an increase inPatient B's appetite seen following the initiation of the combinationtreatment, the Focalin XR dose was raised to 30 mg at day 1279 andshortly thereafter, the CGI-S score dropped to 2 as seen in FIG. 7,while the patient's weight continued to increase reaching a maximalamount as seen in FIG. 6. Through the use of Periactin, Patient B wasable to increase the dose of Focalin XR without a concomitant loss ofappetite, thus allowing Patient B's attentiveness to be increased.

Example 6: Patient C

Patient C was a male who was 9 years and approximately 3 months whentreatment for ADHD was initiated. Patient C was administered 36 mg ofConcerta at the initiation of treatment for ADHD. Initially, there waslittle weight gain followed by weight loss as shown in FIG. 8. On day350 following the initiation of treatment with Concerta for ADHD,Patient C began a combination treatment that included both Concerta at36 mg and Periactin at 4 mg b.i.d. Following initiation of combinationtherapy, Patient C began to gain weight as shown in FIG. 8, with adecrease in their CGI-S score from 5 to 4 as shown in FIG. 9.

Example 7: Patient D

Patient D was a male who was 7 years and approximately 1 month whentreatment for ADHD was initiated. Patient D was administered 18 mg ofConcerta at the initiation of treatment for ADHD. On day 23 followingthe initiation of treatment with Concerta for ADHD, Patient D began acombination treatment that included both Concerta at 18 mg and Periactinat 2 mg administered in the morning. Following initiation of combinationtherapy, Patient D began to gain weight at an accelerated pace as shownin FIG. 10, with a drop in Patient D's CGI-S score from 6 to 5 as shownin FIG. 11. With the increase in weight gain resultant from thecombination treatment, Patient D was able to have the dose of Concertaincreased to 27 mg, which resulted in Patient D's CGI-S score droppingagain from 5 to 4 as shown in FIG. 11, with only a slight decrease inthe ability of Patient D to continue to gain weight. In addition, thoughthe change lagged the initiation of administration of Periactin toPatient D, the combination treatment also increased the growth rate inPatient D's height, even after the dose of Concerta was increased asseen in FIG. 10. Through the use of Periactin, Patient D was able toincrease the dose of Concerta without a concomitant loss of appetite,thus allowing Patient D's attentiveness to be increased.

Example 8: Patient E

Patient E was a male who was 11 years and approximately two weeks whentreatment for ADHD was initiated. Patient E was administered 27 mg ofConcerta at the initiation of treatment for ADHD and then switched to adose of 10 mg of Focalin XR on day 119 after initiation of treatment.Patient E was then switched to a dose of 15 mg of Focalin XR on day 162after initiation of treatment. Increasing the dose of Focalin XR reducedPatient E's CGI-S score from 6 to 5 as shown in FIG. 13, with noadditional improvement. Additionally, Patient E's weight did notincrease substantively during this time as shown in FIG. 12. On day 23following the initiation of treatment with Concerta and then Focalin XRfor ADHD, Patient E began a combination treatment that included bothFocalin XR at a higher dose of 20 mg and Periactin at 4 mg administeredin the morning. Following initiation of combination therapy, Patient Ebegan to gain weight at an accelerated pace as shown in FIG. 12, whichincreased when Periactin was administered b.i.d. on day 836 followinginitiation of therapy. In addition, Patient E's CGI-S score dropped from5 to 4 following the addition of Periactin to the combination treatmentand then from 4 to 3 when the Periactin was dosed b.i.d. Through the useof Periactin, Patient E was able to increase the dose of Focalin XRwithout a concomitant loss of appetite, thus allowing Patient E'sattentiveness to be increased.

Example 9: Patient F

Patient F was a male who was 6 years and approximately 10 months whentreatment for ADHD was initiated. Patient F was administered Ritalin LAat a dose of 20 mg and Focalin at a dose of 5 mg at the initiation oftreatment for ADHD and then switched to Ritalin LA at a dose of 30 mgand Focalin at a dose of 5 mg on day 46 after initiation of treatment.Patient F was then switched to a Daytrana patch at a dose of 15 mg onday 469 and then increased to a dose of 20 mg on day 606 afterinitiation of treatment. Increasing the dose of Ritalin LA and thenswitching to a Daytrana patch reduced Patient F's CGI-S score from 7 to6 and then 6 to 5 as shown in FIG. 15, with no additional improvement.Additionally, Patient F's weight did not increase substantively duringthis time as shown in FIG. 14. On day 1547 following the initiation oftreatment for ADHD, Patient F began a combination treatment thatincluded both a Daytrana patch, now at a increased dose of 30 mg andPeriactin at 2 mg administered b.i.d. Following initiation ofcombination therapy, Patient F began to gain weight at an acceleratedpace as shown in FIG. 14, which increased when the dose of Periactin wasincreased to 4 mg b.i.d. on day 1950 following the initiation oftherapy. Through the use of Periactin, Patient F was able to increasethe dose of the Daytrana patch without a concomitant loss of appetite,thus allowing Patient F's attentiveness to be increased.

Example 10: Patient G

Patient G was a male who was 8 years and approximately 10 months whentreatment for ADHD was initiated. Patient G was administered 15 mg ofFocalin XR at the initiation of treatment for ADHD. Following initiationof treatment, Patient G's CGI-S score dropped from 5 to 4 as seen inFIG. 17. On day 546 following the initiation of treatment with FocalinXR for ADHD, Patient G began a combination treatment that included bothFocalin XR at 15 mg and Periactin at 4 mg administered b.i.d. Followinginitiation of combination therapy, Patient G began to gain height at anaccelerated pace and continued to gain weight at a good pace as shown inFIG. 16, with a drop in Patient G's CGI-S score from 4to 3 as shown inFIG. 17. With the results seen in FIGS. 16 and 17, Patient G, the doseof Periactin administered to Patient G was decreased to 2 mg b.i.d.

Example 11: Patient H

Patient H was a male who was 11 years and approximately 6 months whentreatment for ADHD was initiated. Patient H was administered 40 mg ofVvyanase at the initiation of treatment for ADHD. There was littleweight gain by Patient H after initiation of treatment as shown in FIG.18, though there was a drop in Patient H's CGI-S score from 6 to 5 asshown in FIG. 19. On day 109 following the initiation of treatment withVvyanase for ADHD, Patient G began a combination treatment that includedboth Vvyanase at 40 mg and Periactin at 2 mg b.i.d. Following initiationof combination therapy, Patient G began to gain weight as shown in FIG.18. Patient H was last seen on day 200 after initiation of treatment forADHD, at which time the CGI-S score had not changed from the prior dateof examination as seen in FIG. 19, though it is understood that anexamination so soon after initiation of combination treatment does notnecessarily mean that Patient H's CGI-S score did not drop further afterday 200 as a result of the increase in caloric intake.

Example 12: Impact of Combination Treatment on ADHD Severity (CGI-S)

CGI-S data for each Patient A-H was plotted together in to allowexamination of the effectiveness of an appetite stimulant, in this case,Periactin, to decrease the CGI-S score of the patients. As the data inFIG. 20 shows, in general, the addition of an appetite simulant to atreatment for ADHD over time lowered the CGI-S of a Patient by at leasta score of 1 as compared to the same patient prior to receipt of theappetite stimulant. This is also shown in FIG. 21. In some cases, thiswas due in part to the ability of the patient to increase the dose ofthe treatment for ADHD following initiation of the combinationtreatment. Overall, combination treatment decreased severity as measuredby CGI-S by 43% versus the baseline and showed a 22% improvement overADHD treatment alone, with a mean CGI-S score of 4.4 with ADHD treatmentalone and 3.4 for combination treatment.

Example 13: Impact of Treatment on Improvement in ADHD

Patients A-H had their CGI-I scores noted at each visit with aclinician. Measurements of the CGI-I scores of Patients A-H found thatthe patients CGI-I scores improved following initiation of a combinationtreatment as shown in FIG. 22. More particularly, patients oncombination treatment had CGI-I scores that showed the patient waseither minimally improved or much improved following treatment ascompared to patients receiving ADHD medication only, several of whomwere minimally worse or showed no change, with none showing muchimproved as shown in FIG. 22. Overall, combination treatment decreasedseverity as measured by CGI-I showed 30% improvement over ADHD treatmentalone, with a mean CGI-S score of 3.4 with ADHD treatment alone and 2.4for combination treatment.

Example 14

The patient is a 34 year old man suffering from chronic migraines. Theman is administered an amphetamine along with a pain killer and theseverity of the migraines are reduced over time, but the appetite of theman is similarly reduced. Over time, while taking the amphetamine andpain killer, the man loses weight and suffers fatigue and a reduction inattentiveness. The man is then administered an appetite stimulant totake with the amphetamine and pain killer. The man's migraines continueto remain significantly reduced over time, but his appetite is restoredand he maintains his weight over the same period of time.

Example 15

The patient is a 42 year old woman suffering from narcolepsy. The womanis administered an amphetamine along with sleep medication and theseverity of the narcolepsy is reduced over time, but the appetite of thewoman is similarly reduced. Over time, while taking the amphetamine andsleep medication, the woman loses weight and suffers fatigue and areduction in attentiveness. The woman is then administered an appetitestimulant to take with the amphetamine and sleep medication. The woman'smigraines continue to remain significantly reduced over time, but herappetite is restored and she maintains his weight over the same periodof time.

A method of treating an individual with a disorder associated with anattention deficit disorder, the method comprises the step ofadministering to an individual in need thereof a pharmaceuticalcomposition which comprises administration of a therapeutic compound totreat the attention deficit disorder and a therapeutic compound to treata reduction in appetite, wherein administration reduces a symptom of adisorder associated with an attention deficit disorder and increases theattentiveness of the individual, thereby treating the individual.

The method of claim 1, wherein the attention deficit disorder isAttention Deficit Hyperactivity Disorder (ADHD).

The method of claim 1, wherein the therapeutic compound administered forthe treatment of an attention deficit disorder is an amphetamine or amethylphenidate.

The method of claim 3, wherein the amphetamine or methylphenidate isselected from the group consisting of OROS methylphenidate (Concerta),dextroamphetamine immediate/sustained release (Adderall/Adderall XR),dexmethylphenidate (Focalin), Focalin XR, Metadate CD, Metadate ER,NWP09, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Spansules,Methylin ER (Ritalin SR), methylphenidate (Ritalin), and methylphenidateCR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv ER,Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch,Methylin chewable, Methylin liquid, Dextrostat, Strattera, Tenex,Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil,Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor,Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor,Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol,Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane,Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, XanaxXR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata,Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol,Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compoundsidentified in Table 1.

The method according to any one of claims 1-4, wherein the symptomsassociated with attention deficit disorder is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claims 1-4, wherein the severityassociated with attention deficit disorder is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claims 1-4, wherein the symptomsassociated with attention deficit disorder is reduced by about about 10%to about 100%, about 20% to about 100%, about 30% to about 100%, about40% to about 100%, about 50% to about 100%, about 60% to about 100%,about 70% to about 100%, about 80% to about 100%, about 10% to about90%, about 20% to about 90%, about 30% to about 90%, about 40% to about90%, about 50% to about 90%, about 60% to about 90%, about 70% to about90%, about 10% to about 80%, about 20% to about 80%, about 30% to about80%, about 40% to about 80%, about 50% to about 80%, or about 60% toabout 80%, about 10% to about 70%, about 20% to about 70%, about 30% toabout 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claims 1-4, wherein the dose of thetherapeutic compound to treat the attention deficit disorder is in therange of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.

The method according to any one of claims 1-4, wherein the dose of thetherapeutic compound to treat the attention deficit disorder is in therange of about 0. 001 mg/kg/day to about 100 mg/kg/day.

The method according to any one of claims 1-4, wherein the dose of thetherapeutic compound to treat the attention deficit disorder is in therange of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to about 20mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to about 35mg/kg/day, about 0.001 mg/kg/day to about 40 mg/kg/day, about 0.001mg/kg/day to about 45 mg/kg/day, about 0.001 mg/kg/day to about 50mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001mg/kg/day to about 100 mg/kg/day.

The method according to any of claims 1-11, wherein the therapeuticcompound to treat the attention deficit disorder is administered to anindividual topical, sublingual, rectal, vaginal, trancutaneous, oral,inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

The method according to any of claims 1-11, wherein the therapeuticcompound to treat the attention deficit disorder is administered as aliquid, a solid, a semi-solid or an aerosol.

The method according to any of claims 1-4, wherein the therapeuticcompound is formulated as a tablet, lozenge, orally dissolved strip,capsule, syrup, oral suspension, emulsion, granule, sprinkle or pellet.

The method of claim 1, wherein the therapeutic compound is a longacting, sustained release, extended release, immediate release, slowrelease, or controlled release therapeutic compound.

The method of claim 14, wherein the therapeutic compound is releasedover a period of about 3 days after administration, about 7 days afteradministration, about 10 days after administration, about 15 days afteradministration, about 20 days after administration, about 25 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration, or about 90 days after administration.

The method of claim 14, wherein the therapeutic compound is releasedover a period of at least 3 days after administration, at least 7 daysafter administration, at least 10 days after administration, at least 15days after administration, at least 20 days after administration, atleast 25 days after administration, at least 30 days afteradministration, at least 45 days after administration, at least 60 daysafter administration, at least 75 days after administration, or at least90 days after administration

The method of claim 14, wherein the therapeutic compound is releasedover a period of about 1 day after administration, about 2 days afteradministration, about 3 days after administration, about 4 days afteradministration, about 5 days after administration, about 6 days afteradministration or about 7 days or more after administration.

The method according to any of claim 1, wherein the pharmaceuticalcomposition includes pharmaceutical acceptable components.

The method of claim 18, wherein the pharmaceutical acceptable componentsis selected from the group consisting of a salt, a surfactant, an aminoacid, a stabilizer or a buffer.

The method of claim 18, wherein the salt is selected from the groupconsisting of citric acid, sodium chloride, potassium chloride, sodiumsulfate, potassium nitrate, sodium phosphate monobasic or sodiumphosphate dibasic.

The method of claim 18, wherein the surfactant is a polysorbate.

The method of claim 21, wherein the polysorbate is selected from thegroup consisting of Tween 20, Tween 80, F68, F88, sorbitain esters,lipids, fatty acids or fatty esters.

The method of claim 1, wherein the therapeutic compound to treat aappetite reduction is an orexigenic drug.

The method of claim 23, wherein the orexigenic drug is selected from thegroup of: alcohol, GHB, and other sedatives such as some benzodiazepineand nonbenzodiazepine tranquilizers and sleeping pills, anti-depressants(some SSRIs, Mianserin, etc.), 5-HT_(2C) receptor antagonists/inverseagonists (e.g., mirtazapine, mianserin, olanzapine, quetiapine,risperidone, amitriptyline, imipramine, cyproheptadine, etc.), H₁receptor antagonists/inverse agonists (e.g., buclizine, mirtazapine,mianserin, olanzapine, quetiapine, n-3 fatty acids, amitriptyline,chlorpheniramine maleate, etc.), D₁/D₂ receptor antagonists (e.g.,haloperidol, chlorpromazine, olanzapine, risperidone, quetiapine, etc.),Marinol, Megace, Megace ES, α₁-adrenergic receptor antagonists (such asdoxazosin, carvedilol, propanolol, colonidine), Serefam, α₂-adrenergicreceptor agonists (e.g., clonidine, guanfacine, etc.), some betablockers such as propanolol, natural or synthetic CB₁ receptor agonists(e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol,diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodiumvalproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabeticdrugs such as glibenclamide and chlorpropamide, steroids (including,without limitation, boldenone, oxymetholone, dexamethasone, ormethandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone,testosterone), some kappa opioid receptor agonists such as tifluadom,hormones such as mederoxyprogesteronemirtazapine (Remeron), atetracyclic antidepressant; cyproheptadine (Periactin), anantihistamine; nandrolone, oxymetholone, and oxandrolone (Anadrol-50,Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptormodulator (“SARM”), Oxandrin, and other brand names), VT-122 (acoadministration of propranolol and etodolac), type 4 melanocortinreceptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoyreceptor, fast skeletal muscle troponin-activating substance,anticatabolic/anabolic transforming agent MT-102, celecoxib,testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIBreceptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fattyacids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). Inaddition to these prescription drugs, fish oil (eicosapentaenoic acid orEPA), EATMOR, other vitamins and natural or artificial appetitestimulants.

The method of claim 23, wherein the orexigenic drug is cyproheptadinehydrochloride.

The method according to any one of claim 1 or 23-25, wherein thesymptoms associated with appetite reduction is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claim 1 or 23-25, wherein thesymptoms associated with appetite reduction is reduced by about 10% toabout 100%, about 20% to about 100%, about 30% to about 100%, about 40%to about 100%, about 50% to about 100%, about 60% to about 100%, about70% to about 100%, about 80% to about 100%, about 10% to about 90%,about 20% to about 90%, about 30% to about 90%, about 40% to about 90%,about 50% to about 90%, about 60% to about 90%, about 70% to about 90%,about 10% to about 80%, about 20% to about 80%, about 30% to about 80%,about 40% to about 80%, about 50% to about 80%, or about 60% to about80%, about 10% to about 70%, about 20% to about 70%, about 30% to about70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 1 or 23-25, wherein thesymptoms associated with reduction in the severity of appetite reductionis reduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95%.

The method according to any one of claim 1 or 23-25, wherein theseverity associated with reduction in appetite is reduced by about 10%to about 100%, about 20% to about 100%, about 30% to about 100%, about40% to about 100%, about 50% to about 100%, about 60% to about 100%,about 70% to about 100%, about 80% to about 100%, about 10% to about90%, about 20% to about 90%, about 30% to about 90%, about 40% to about90%, about 50% to about 90%, about 60% to about 90%, about 70% to about90%, about 10% to about 80%, about 20% to about 80%, about 30% to about80%, about 40% to about 80%, about 50% to about 80%, or about 60% toabout 80%, about 10% to about 70%, about 20% to about 70%, about 30% toabout 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 1 or 23-25, wherein thetreatment for appetite reduction results in an increase in weight by atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95%.

The method according to any one of alcims 1 or 23-25, wherein thetreatment for appetite reduction results in an increase in weight byabout 10% to about 100%, about 20% to about 100%, about 30% to about100%, about 40% to about 100%, about 50% to about 100%, about 60% toabout 100%, about 70% to about 100%, about 80% to about 100%, about 10%to about 90%, about 20% to about 90%, about 30% to about 90%, about 40%to about 90%, about 50% to about 90%, about 60% to about 90%, about 70%to about 90%, about 10% to about 80%, about 20% to about 80%, about 30%to about 80%, about 40% to about 80%, about 50% to about 80%, or about60% to about 80%, about 10% to about 70%, about 20% to about 70%, about30% to about 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 1 or 23-25, wherein thetreatment for appetite reduction results in an increase in height by atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95%.

The method according to any one of claim 1 or 23-25, wherein thetreatment for appetite reduction results in an increase in weight by atleast 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, atleast 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, atleast 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds,at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, atleast 25 pounds, at least 30 pounds, at least 50 pounds. In anotherembodiment, a therapeutic compound disclosed herein for the treatment ofappetite reduction results in an increase in weight by, e.g., from 0.5pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 poundsto 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to tenpounds, from 2 pounds to 7.5 pounds.

The method according to any of claim 1 or 23-25, wherein the treatmentfor appetite reduction increases the attentiveness of a patient by atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95%.

The method according to any of claim 1 or 23-25, wherein the treatmentfor appetite reduction increases the attentiveness of a patient by about10% to about 100%, about 20% to about 100%, about 30% to about 100%,about 40% to about 100%, about 50% to about 100%, about 60% to about100%, about 70% to about 100%, about 80% to about 100%, about 10% toabout 90%, about 20% to about 90%, about 30% to about 90%, about 40% toabout 90%, about 50% to about 90%, about 60% to about 90%, about 70% toabout 90%, about 10% to about 80%, about 20% to about 80%, about 30% toabout 80%, about 40% to about 80%, about 50% to about 80%, or about 60%to about 80%, about 10% to about 70%, about 20% to about 70%, about 30%to about 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 1 or 23-35, wherein the dose ofthe therapeutic compound to treat the reduction in appetite is in therange of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.

The method according to any one of claim 1 or 23-35, wherein the dose ofthe therapeutic compound to treat reduction in appetite is in the rangeof about 0. 001 mg/kg/day to about 100 mg/kg/day.

The method according to any one of claim 1 or 23-35, wherein the dose ofthe therapeutic compound to treat the reduction in appetite is in therange of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to about 20mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to about 35mg/kg/day, about 0.001 mg/kg/day to about 40 mg/kg/day, about 0.001mg/kg/day to about 45 mg/kg/day, about 0.001 mg/kg/day to about 50mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001mg/kg/day to about 100 mg/kg/day.

The method according to any of claim 1 or 23-25, wherein the therapeuticcompound to treat the reduction in appetite is administered to anindividual topical, sublingual, rectal, vaginal, trancutaneous, oral,inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound to treat the reduction in appetite is administered as a liquid,a solid, a semi-solid or an aerosol.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is formulated as a tablet, lozenge, orally dissolved strip,capsule, syrup, oral suspension, emulsion, granule, sprinkle or pellet.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is a long acting, sustained release, extended release,immediate release, slow release, or controlled release therapeuticcompound.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is released over a period of about 3 days after administration,about 7 days after administration, about 10 days after administration,about 15 days after administration, about 20 days after administration,about 25 days after administration, about 30 days after administration,about 45 days after administration, about 60 days after administration,about 75 days after administration, or about 90 days afteradministration.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is released over a period of at least 3 days afteradministration, at least 7 days after administration, at least 10 daysafter administration, at least 15 days after administration, at least 20days after administration, at least 25 days after administration, atleast 30 days after administration, at least 45 days afteradministration, at least 60 days after administration, at least 75 daysafter administration, or at least 90 days after administration

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is released over a period of about 1 day after administration,about 2 days after administration, about 3 days after administration,about 4 days after administration, about 5 days after administration,about 6 days after administration or about 7 days or more afteradministration.

The method according to any of claim 1 or 23-35, wherein thepharmaceutical composition includes pharmaceutical acceptablecomponents.

The method of claim 46, wherein the pharmaceutical acceptable componentsis selected from the group consisting of a salt, a surfactant, an aminoacid, a stabilizer or a buffer.

The method of claim 47, wherein the salt is selected from the groupconsisting of citric acid, sodium chloride, potassium chloride, sodiumsulfate, potassium nitrate, sodium phosphate monobasic or sodiumphosphate dibasic.

The method of claim 46, wherein the surfactant is a polysorbate.

The method of claim 49, wherein the polysorbate is selected from thegroup consisting of Tween 20, Tween 80, F68, F88, sorbitain esters,lipids, fatty acids or fatty esters.

The method of claim 1, wherein the increase in attentiveness by anindividual is measured by CGI-S.

The method of claim 51, wherein the CGI-S scale is from 1 to 7.

The method of claim 52, wherein a measurement of 7 identifies anindividual that is extremely ill, 6 identifies an individual that isseverely ill, 5 identifies an individual that is markedly ill, 4identifies an individual that is moderately ill, 3 identifies anindividual that is mildly ill, 2 identifies an individual that isborderline ill and a measurement of 1 identifies an individual that isnormal.

The method of any of claim 1 or 51-53, wherein the increase inattentiveness measured by CGI-S is by a reduction in the score by 1 ormore as compared to a patient not receiving a therapeutic compound totreat a appetite reduction.

The method of any of claim 1 or 51-53, wherein the patient's CGI-S scoreis reduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95%.

The method of any of claim 1 or 51-53, wherein the patient's CGI-S scoreis reduced by about 10% to about 100%, about 20% to about 100%, about30% to about 100%, about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, about 10% to about 90%, about 20% to about 90%, about 30% to about90%, about 40% to about 90%, about 50% to about 90%, about 60% to about90%, about 70% to about 90%, about 10% to about 80%, about 20% to about80%, about 30% to about 80%, about 40% to about 80%, about 50% to about80%, or about 60% to about 80%, about 10% to about 70%, about 20% toabout 70%, about 30% to about 70%, about 40% to about 70%, or about 50%to about 70%.

The method of claim 1, wherein the increase in attentiveness by anindividual is measured by CGI-I.

The method of claim 57, wherein the CGI-I scale is from 1 to 7.

The method of claim 58, wherein a measurement of 7 identifies anindividual that is very much worse, 6 identifies an individual that ismuch worse, 5 identifies an individual that is minimally worse, 4identifies an individual that is no change, 3 identifies an individualthat is minimally improved, 2 identifies an individual that is muchimproved and a measurement of 1 identifies an individual that is verymuch improved.

The method of any of claim 1 or 57-59, wherein the increase inattentiveness measured CGI-I is by a reduction in the score by 1 or moreas compared to a patient not receiving a therapeutic compound to treat areduction in appetite.

The method of any of claim 1 or 57-59, wherein the patient's CGI-S scoreis reduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95%.

The method of any of claim 1 or 57-59, wherein the patient's CGI-S scoreis reduced by about 10% to about 100%, about 20% to about 100%, about30% to about 100%, about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, about 10% to about 90%, about 20% to about 90%, about 30% to about90%, about 40% to about 90%, about 50% to about 90%, about 60% to about90%, about 70% to about 90%, about 10% to about 80%, about 20% to about80%, about 30% to about 80%, about 40% to about 80%, about 50% to about80%, or about 60% to about 80%, about 10% to about 70%, about 20% toabout 70%, about 30% to about 70%, about 40% to about 70%, or about 50%to about 70%.

The method of claim 1, wherein the increase in attentiveness by anindividual is measured by the p academic performance rating scale, ADDevaluation scale-3^(rd) edition (ADDES-3), ADHD rating scale-IV(ADHD-RS-IV), youth self report (broadband instrument), Conners parentrating scale-revised (CPRS-R), Conners teacher rating scale-revised(CTRS-R), Conners 3 self-reporting scale (Conner 3-SR; ages 8-18y), homesituations questionnaire-revised, inattention/overactivity withaggression (IOWA) Conners teacher's rating scale, Swanson Nolan andPelham IV scale (SNAP-IV), Swanson Kotkin Agler M-Flynn and Pelham(SKAMP), Vanderbilt ADHD diagnostic parent rating scale (VADPRS),Vanderbilt ADHD diagnostic teacher rating scale (VADTRS), behaviorassessment system for children-2^(nd) edition (BASC-2) or the Connersrating scale long version.

A pharmaceutical composition comprising a therapeutic compound for adisorder associated with an attention deficit disorder and a therapeuticcompound for a disorder associated with a reduction in appetite, whereinthe pharmaceutical composition reduces a symptom of a disorderassociated with an attention deficit disorder and increases theattentiveness of the individual, thereby treating the individual.

A pharmaceutical composition of claim 64, wherein the attention deficitdisorder is Attention Deficit Hyperactivity Disorder (ADHD).

A pharmaceutical composition of claim 64, wherein the therapeuticcompound administered for the treatment of an attention deficit disorderis an amphetamine or a methylphenidate.

A pharmaceutical composition of claim 66, wherein the amphetamine ormethylphenidate is selected from the group consisting of OROSmethylphenidate (Concerta), dextroamphetamine immediate/sustainedrelease (Adderall/Adderall XR), dexmethylphenidate (Focalin), FocalinXR, Metadate CD, Metadate ER, NWP09, Dexedrine, dextroamphetamine(Dexedrine), Dexedrine Spansules, Methylin ER (Ritalin SR),methylphenidate (Ritalin), and methylphenidate CR, Ritalin, Ritalin LA,SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Daytrana,Equasym, Dixirit, Kapvay, Daytrana Patch, Methylin chewable, Methylinliquid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTS patch,Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa,Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil,Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, Remeron,Cymbalta, Nardil, Parnate, Emsam patch, Haldol, Orap, Prolixin,Mellaril, Thorazine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa,Seroquel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan,Buspar, Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid,Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, Topamax,Neurontin and the therapeutic compounds identified in Table 1.

A pharmaceutical composition according to any one of claims 64-67,wherein the symptoms associated with attention deficit disorder isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 64-67,wherein the severity associated with attention deficit disorder isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 64-67,wherein the symptoms associated with attention deficit disorder isreduced by about about 10% to about 100%, about 20% to about 100%, about30% to about 100%, about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, about 10% to about 90%, about 20% to about 90%, about 30% to about90%, about 40% to about 90%, about 50% to about 90%, about 60% to about90%, about 70% to about 90%, about 10% to about 80%, about 20% to about80%, about 30% to about 80%, about 40% to about 80%, about 50% to about80%, or about 60% to about 80%, about 10% to about 70%, about 20% toabout 70%, about 30% to about 70%, about 40% to about 70%, or about 50%to about 70%.

A pharmaceutical composition according to any one of claims 64-67,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of at least 0.001 mg/kg/day, at least0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50mg/kg/day.

A pharmaceutical composition according to any one of claims 64-67,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of about 0. 001 mg/kg/day to about 100mg/kg/day.

A pharmaceutical composition according to any one of claims 64-67,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of about 0.001 mg/kg/day to about 10mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day.

A pharmaceutical composition according to any one of claims 64-67,wherein the therapeutic compound to treat the attention deficit disorderis administered to an individual topical, sublingual, rectal, vaginal,trancutaneous, oral, inhaled, intranasal, subcutaneous, intravenous,enteral or parenteral.

A pharmaceutical composition according to any one of claims 64-67,wherein the therapeutic compound to treat the attention deficit disorderis administered as a liquid, a solid, a semi-solid or an aerosol.

A pharmaceutical composition according to any one of claims 64-67,wherein the therapeutic compound is formulated as a tablet, lozenge,orally dissolved strip, capsule, syrup, oral suspension, emulsion,granule, sprinkle or pellet.

A pharmaceutical composition according to claim 64, wherein thetherapeutic compound is a long acting, sustained release, extendedrelease, immediate release, slow release, or controlled releasetherapeutic compound.

A pharmaceutical composition according to claim 77, wherein thetherapeutic compound is released over a period of about 3 days afteradministration, about 7 days after administration, about 10 days afteradministration, about 15 days after administration, about 20 days afteradministration, about 25 days after administration, about 30 days afteradministration, about 45 days after administration, about 60 days afteradministration, about 75 days after administration, or about 90 daysafter administration.

A pharmaceutical composition according to claim 77, wherein thetherapeutic compound is released over a period of at least 3 days afteradministration, at least 7 days after administration, at least 10 daysafter administration, at least 15 days after administration, at least 20days after administration, at least 25 days after administration, atleast 30 days after administration, at least 45 days afteradministration, at least 60 days after administration, at least 75 daysafter administration, or at least 90 days after administration

A pharmaceutical composition according to claim 77, wherein thetherapeutic compound is released over a period of about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, about 6 days after administration or about 7 days ormore after administration.

A pharmaceutical composition according to claim 1, wherein thepharmaceutical composition includes pharmaceutical acceptablecomponents.

A pharmaceutical composition according to claim8 1, wherein thepharmaceutical acceptable components is selected from the groupconsisting of a salt, a surfactant, an amino acid, a stabilizer or abuffer.

A pharmaceutical composition according to claim 82, wherein the salt isselected from the group consisting of citric acid, sodium chloride,potassium chloride, sodium sulfate, potassium nitrate, sodium phosphatemonobasic or sodium phosphate dibasic.

A pharmaceutical composition according to 81, wherein the surfactant isa polysorbate.

A pharmaceutical composition according to claim 84, wherein thepolysorbate is selected from the group consisting of Tween 20, Tween 80,F68, F88, sorbitain esters, lipids, fatty acids or fatty esters.

A pharmaceutical composition according to claim 64, wherein thetherapeutic compound to treat a appetite reduction is an orexigenicdrug.

A pharmaceutical composition according to claim 86, wherein theorexigenic drug is selected from the group of: alcohol, GHB, and othersedatives such as some benzodiazepine and nonbenzodiazepinetranquilizers and sleeping pills, anti-depressants (some SSRIs,Mianserin, etc.), 5-HT_(2C) receptor antagonists/inverse agonists (e.g.,mirtazapine, mianserin, olanzapine, quetiapine, risperidone,amitriptyline, imipramine, cyproheptadine, etc.), H₁ receptorantagonists/inverse agonists (e.g., buclizine, mirtazapine, mianserin,olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlorpheniraminemaleate, etc.), D₁/D₂ receptor antagonists (e.g., haloperidol,chlorpromazine, olanzapine, risperidone, quetiapine, etc.), Marinol,Megace, Megace ES, α₁-adrenergic receptor antagonists (such asdoxazosin, carvedilol, propanolol, colonidine), Serefam, α₂-adrenergicreceptor agonists (e.g., clonidine, guanfacine, etc.), some betablockers such as propanolol, natural or synthetic CB₁ receptor agonists(e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol,diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodiumvalproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabeticdrugs such as glibenclamide and chlorpropamide, steroids (including,without limitation, boldenone, oxymetholone, dexamethasone, ormethandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone,testosterone), some kappa opioid receptor agonists such as tifluadom,hormones such as mederoxyprogesteronemirtazapine (Remeron), atetracyclic antidepressant; cyproheptadine (Periactin), anantihistamine; nandrolone, oxymetholone, and oxandrolone (Anadrol-50,Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptormodulator (“SARM”), Oxandrin, and other brand names), VT-122 (acoadministration of propranolol and etodolac), type 4 melanocortinreceptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoyreceptor, fast skeletal muscle troponin-activating substance,anticatabolic/anabolic transforming agent MT-102, celecoxib,testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIBreceptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fattyacids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). Inaddition to these prescription drugs, fish oil (eicosapentaenoic acid orEPA), EATMOR, other vitamins and natural or artificial appetitestimulants.

A pharmaceutical composition according to claim 87, wherein theorexigenic drug is cyproheptadine hydrochloride.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the symptoms associated with appetite reduction isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the symptoms associated with appetite reduction isreduced by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the symptoms associated with reduction in the severity ofappetite reduction is reduced by at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90% or at least95%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the severity associated with reduction in appetite isreduced by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction results in anincrease in weight by at least 10%, at least 15%, at least 20%, at least25%, at least 30%, at least 35%, at least 40%, at least 45%, at least50%, at least 55%, at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction results in anincrease in weight by about 10% to about 100%, about 20% to about 100%,about 30% to about 100%, about 40% to about 100%, about 50% to about100%, about 60% to about 100%, about 70% to about 100%, about 80% toabout 100%, about 10% to about 90%, about 20% to about 90%, about 30% toabout 90%, about 40% to about 90%, about 50% to about 90%, about 60% toabout 90%, about 70% to about 90%, about 10% to about 80%, about 20% toabout 80%, about 30% to about 80%, about 40% to about 80%, about 50% toabout 80%, or about 60% to about 80%, about 10% to about 70%, about 20%to about 70%, about 30% to about 70%, about 40% to about 70%, or about50% to about 70%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction results in anincrease in height by at least 10%, at least 15%, at least 20%, at least25%, at least 30%, at least 35%, at least 40%, at least 45%, at least50%, at least 55%, at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction results in anincrease in weight by at least 0.5 pounds, at least 1 pound, at least1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least 3 pounds,at least 3.5 pounds, at least 4 pounds, at least 4.5 pounds, at least 5pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, atleast 7 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5pounds, at least 9 pounds, at least 9.5 pounds, at least 10 pounds, atleast 10.5 pounds, at least 11 pounds, at least 11.5 pounds, at least 12pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 pounds,at least 14 pounds, at least 14.5 pounds, at least 15 pounds, at least20 pounds, at least 25 pounds, at least 30 pounds, at least 50 pounds.In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction results in an increase in weight by,e.g., from 0.5 pounds to 50 pounds, from 0.5 pounds to 30 pounds, from0.5 pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 poundsto 15 pounds, from 0.5 pounds to ten pounds, from 0.5 pounds to 7.5pounds, from 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 pound to 5pounds, from 2 pounds to ten pounds, from 2 pounds to 7.5 pounds.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction increases theattentiveness of a patient by at least 10%, at least 15%, at least 20%,at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, atleast 50%, at least 55%, at least 60%, at least 65%, at least 70%, atleast 75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the treatment for appetite reduction increases theattentiveness of a patient by about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the dose of the therapeutic compound to treat thereduction in appetite is in the range of at least 0.001 mg/kg/day, atleast 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, atleast 5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, atleast 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, atleast 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or atleast 50 mg/kg/day.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the dose of the therapeutic compound to treat reductionin appetite is in the range of about 0. 001 mg/kg/day to about 100mg/kg/day.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the dose of the therapeutic compound to treat thereduction in appetite is in the range of about 0.001 mg/kg/day to about10 mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day.

A pharmaceutical composition according to any one of claims 64 and86-88, wherein the therapeutic compound to treat the reduction inappetite is administered to an individual topical, sublingual, rectal,vaginal, trancutaneous, oral, inhaled, intranasal, subcutaneous,intravenous, enteral or parenteral.

A pharmaceutical composition according to any one of claims 64 and86-102, wherein the therapeutic compound to treat the reduction inappetite is administered as a liquid, a solid, a semi-solid or anaerosol.

A pharmaceutical composition according to any one of claims 64 and86-102, wherein the therapeutic compound is formulated as a tablet,lozenge, orally dissolved strip, capsule, syrup, oral suspension,emulsion, granule, sprinkle or pellet.

A pharmaceutical composition according to any one of claims 64 and86-103, wherein the therapeutic compound is a long acting, sustainedrelease, extended release, immediate release, slow release, orcontrolled release therapeutic compound.

A pharmaceutical composition according to any one of claims 64 and86-103, wherein the therapeutic compound is released over a period ofabout 3 days after administration, about 7 days after administration,about 10 days after administration, about 15 days after administration,about 20 days after administration, about 25 days after administration,about 30 days after administration, about 45 days after administration,about 60 days after administration, about 75 days after administration,or about 90 days after administration.

A pharmaceutical composition according to any one of claims 64 and86-103, wherein the therapeutic compound is released over a period of atleast 3 days after administration, at least 7 days after administration,at least 10 days after administration, at least 15 days afteradministration, at least 20 days after administration, at least 25 daysafter administration, at least 30 days after administration, at least 45days after administration, at least 60 days after administration, atleast 75 days after administration, or at least 90 days afteradministration

A pharmaceutical composition according to any one of claims 64 and86-103, wherein the therapeutic compound is released over a period ofabout 1 day after administration, about 2 days after administration,about 3 days after administration, about 4 days after administration,about 5 days after administration, about 6 days after administration orabout 7 days or more after administration.

A pharmaceutical composition according to any one of claims 64 and86-108, wherein the pharmaceutical composition includes pharmaceuticalacceptable components.

A pharmaceutical composition according to claim 109, wherein thepharmaceutical acceptable components is selected from the groupconsisting of a salt, a surfactant, an amino acid, a stabilizer or abuffer.

A pharmaceutical composition according to claim 110, wherein the salt isselected from the group consisting of citric acid, sodium chloride,potassium chloride, sodium sulfate, potassium nitrate, sodium phosphatemonobasic or sodium phosphate dibasic.

A pharmaceutical composition according to claim 110, wherein thesurfactant is a polysorbate.

A pharmaceutical composition according to claim 112, wherein thepolysorbate is selected from the group consisting of Tween 20, Tween 80,F68, F88, sorbitain esters, lipids, fatty acids or fatty esters.

A pharmaceutical composition according to claim 64, wherein the increasein attentiveness by an individual is measured by CGI-S.

A pharmaceutical composition according to claim 114, wherein the CGI-Sscale is from 1 to 7.

A pharmaceutical composition according to claim 115, wherein ameasurement of 7 identifies an individual that is extremely ill, 6identifies an individual that is severely ill, 5 identifies anindividual that is markedly ill, 4 identifies an individual that ismoderately ill, 3 identifies an individual that is mildly ill, 2identifies an individual that is borderline ill and a measurement of 1identifies an individual that is normal.

A pharmaceutical composition according to any of claim 64 or 114-116,wherein the increase in attentiveness measured by CGI-S is by areduction in the score by 1 or more as compared to a patient notreceiving a therapeutic compound to treat a appetite reduction.

A pharmaceutical composition according to any of claim 64 or 114-116,wherein the patient's CGI-S score is reduced by at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90% or at least 95%.

A pharmaceutical composition according to any of claim 64 or 114-116,wherein the patient's CGI-S score is reduced by about 10% to about 100%,about 20% to about 100%, about 30% to about 100%, about 40% to about100%, about 50% to about 100%, about 60% to about 100%, about 70% toabout 100%, about 80% to about 100%, about 10% to about 90%, about 20%to about 90%, about 30% to about 90%, about 40% to about 90%, about 50%to about 90%, about 60% to about 90%, about 70% to about 90%, about 10%to about 80%, about 20% to about 80%, about 30% to about 80%, about 40%to about 80%, about 50% to about 80%, or about 60% to about 80%, about10% to about 70%, about 20% to about 70%, about 30% to about 70%, about40% to about 70%, or about 50% to about 70%.

A pharmaceutical composition according to claim 64, wherein the increasein attentiveness by an individual is measured on by CGI-I.

A pharmaceutical composition according to claim 120, wherein the CGI-Iscale is from 1 to 7.

A pharmaceutical composition according to claim 121, wherein ameasurement of 7 identifies an individual that is very much worse, 6identifies an individual that is much worse, 5 identifies an individualthat is minimally worse, 4 identifies an individual that is no change, 3identifies an individual that is minimally improved, 2 identifies anindividual that is much improved and a measurement of 1 identifies anindividual that is very much improved.

A pharmaceutical composition according to any of claim 64 or 120-122,wherein the increase in attentiveness measured CGI-I is by a reductionin the score by 1 or more as compared to a patient not receiving atherapeutic compound to treat a reduction in appetite.

A pharmaceutical composition according to any of claim 64 or 120-122,wherein the patient's CGI-S score is reduced by at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90% or at least 95%.

A pharmaceutical composition according to any of claim 64 or 120-122,wherein the patient's CGI-S score is reduced by about 10% to about 100%,about 20% to about 100%, about 30% to about 100%, about 40% to about100%, about 50% to about 100%, about 60% to about 100%, about 70% toabout 100%, about 80% to about 100%, about 10% to about 90%, about 20%to about 90%, about 30% to about 90%, about 40% to about 90%, about 50%to about 90%, about 60% to about 90%, about 70% to about 90%, about 10%to about 80%, about 20% to about 80%, about 30% to about 80%, about 40%to about 80%, about 50% to about 80%, or about 60% to about 80%, about10% to about 70%, about 20% to about 70%, about 30% to about 70%, about40% to about 70%, or about 50% to about 70%.

A pharmaceutical composition according to claim 64, wherein the increasein attentiveness by an individual is measured by the p academicperformance rating scale, ADD evaluation scale-3^(rd) edition (ADDES-3),ADHD rating scale-IV (ADHD-RS-IV), youth self report (broadbandinstrument), Conners parent rating scale-revised (CPRS-R), Connersteacher rating scale-revised (CTRS-R), Conners 3 self-reporting scale(Conner 3-SR; ages 8-18y), home situations questionnaire-revised,inattention/overactivity with aggression (IOWA) Conners teacher's ratingscale, Swanson Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin AglerM-Flynn and Pelham (SKAMP), Vanderbilt ADHD diagnostic parent ratingscale (VADPRS), Vanderbilt ADHD diagnostic teacher rating scale(VADTRS), behavior assessment system for children-2^(nd) edition(BASC-2) or the Conners rating scale long version.

A method of treating an individual with a disorder associated with apsychological and/or neurological disorder, the method comprises thestep of administering to an individual in need thereof a pharmaceuticalcomposition which comprises a therapeutic compound consisting of anamphetamine and/or a methylphenidate and a therapeutic compound to treata reduction in appetite, thereby treating the individual.

The method of claim 127, wherein, the psychological and/or neurologicaldisorder is selected from the group of migraine, anti-serotonergic sideeffects, narcolepsy, excessive sleepiness associated with shift work,obstructive sleep apnea as an adjunct to continuous positive airwayspressure (“CPAP”), exogenous obesity, disruptive behaviour disorderincluding oppositional defiant disorder (“ODD”) and conduct disorder(“CD”), obesity, depression (including, without limitation, augmentationof antidepressants in treating refractory depression and cancer-relateddepression), neural insult, fatigue (including, without limitation,disease-related fatigue in patients with HIV, advanced cancer, multiplesclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitisC), lethargy, binge eating disorder, schizophrenia, sleep cycledisorder, cocaine addiction, Parkinson's Disease, combat and non-combatrelated PTSD and/or tic.

The method of claim 127, wherein the therapeutic compound to treatphychological or neurological disorder is an amphetamine ormethylphenidate.

The method of claim 129, wherein the amphetamine or methylphenidate isselected from the group consisting of OROS methylphenidate (Concerta),dextroamphetamine immediate/sustained release (Adderall/Adderall XR),dexmethylphenidate (Focalin), Focalin XR, Metadate CD, Metadate ER,NWP09, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Spansules,Methylin ER (Ritalin SR), methylphenidate (Ritalin), and methylphenidateCR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv ER,Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, Daytrana Patch,Methylin chewable, Methylin liquid, Dextrostat, Strattera, Tenex,Catapres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, Paxil,Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor,Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor,Effexor XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol,Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxitane,Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Clozaril, Xanax, XanaxXR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, Sonata,Rozerem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carbatrol,Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compoundsidentified in Table 1.

The method according to any one of claims 127-130, wherein the symptomsassociated with attention deficit disorder is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claims 127-130, wherein the severityassociated with attention deficit disorder is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claims 127-130, wherein the symptomsassociated with attention deficit disorder is reduced by about about 10%to about 100%, about 20% to about 100%, about 30% to about 100%, about40% to about 100%, about 50% to about 100%, about 60% to about 100%,about 70% to about 100%, about 80% to about 100%, about 10% to about90%, about 20% to about 90%, about 30% to about 90%, about 40% to about90%, about 50% to about 90%, about 60% to about 90%, about 70% to about90%, about 10% to about 80%, about 20% to about 80%, about 30% to about80%, about 40% to about 80%, about 50% to about 80%, or about 60% toabout 80%, about 10% to about 70%, about 20% to about 70%, about 30% toabout 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claims 127-130, wherein the dose ofthe therapeutic compound to treat the attention deficit disorder is inthe range of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.

The method according to any one of claims 127-130, wherein the dose ofthe therapeutic compound to treat the attention deficit disorder is inthe range of about 0.001 mg/kg/day to about 100 mg/kg/day.

The method according to any one of claims 127-130, wherein the dose ofthe therapeutic compound to treat the attention deficit disorder is inthe range of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to about 20mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to about 35mg/kg/day, about 0.001 mg/kg/day to about 40 mg/kg/day, about 0.001mg/kg/day to about 45 mg/kg/day, about 0.001 mg/kg/day to about 50mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001mg/kg/day to about 100 mg/kg/day.

The method according to any of claims 127-136, wherein the therapeuticcompound to treat the attention deficit disorder is administered to anindividual topical, sublingual, rectal, vaginal, trancutaneous, oral,inhaled, intranasal, subcutaneous, intravenous, enteral or parenteral.

The method according to any of claims 127-136, wherein the therapeuticcompound to treat the attention deficit disorder is administered as aliquid, a solid, a semi-solid or an aerosol.

The method according to any of claims 127-130, wherein the therapeuticcompound is formulated as a tablet, lozenge, orally dissolved strip,capsule, syrup, oral suspension, emulsion, granule, sprinkle or pellet.

The method of claim 127, wherein the therapeutic compound is a longacting, sustained release, extended release, immediate release, slowrelease, or controlled release therapeutic compound.

The method of claim 140, wherein the therapeutic compound is releasedover a period of about 3 days after administration, about 7 days afteradministration, about 10 days after administration, about 15 days afteradministration, about 20 days after administration, about 25 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration, or about 90 days after administration.

The method of claim 140, wherein the therapeutic compound is releasedover a period of at least 3 days after administration, at least 7 daysafter administration, at least 10 days after administration, at least 15days after administration, at least 20 days after administration, atleast 25 days after administration, at least 30 days afteradministration, at least 45 days after administration, at least 60 daysafter administration, at least 75 days after administration, or at least90 days after administration

The method of claim 140, wherein the therapeutic compound is releasedover a period of about 1 day after administration, about 2 days afteradministration, about 3 days after administration, about 4 days afteradministration, about 5 days after administration, about 6 days afteradministration or about 7 days or more after administration.

The method according to any of claim 127, wherein the pharmaceuticalcomposition includes pharmaceutical acceptable components.

The method of claim 144, wherein the pharmaceutical acceptablecomponents is selected from the group consisting of a salt, asurfactant, an amino acid, a stabilizer or a buffer.

The method of claim 145, wherein the salt is selected from the groupconsisting of citric acid, sodium chloride, potassium chloride, sodiumsulfate, potassium nitrate, sodium phosphate monobasic or sodiumphosphate dibasic.

The method of claim 144, wherein the surfactant is a polysorbate.

The method of claim 147, wherein the polysorbate is selected from thegroup consisting of Tween 20, Tween 80, F68, F88, sorbitain esters,lipids, fatty acids or fatty esters.

The method of claim 127, wherein the therapeutic compound to treat anappetite reduction is an orexigenic drug.

The method of claim 149, wherein the orexigenic drug is selected fromthe group of: alcohol, GHB, and other sedatives such as somebenzodiazepine and nonbenzodiazepine tranquilizers and sleeping pills,anti-depressants (some SSRIs, Mianserin, etc.), 5-HT_(2C) receptorantagonists/inverse agonists (e.g., mirtazapine, mianserin, olanzapine,quetiapine, risperidone, amitriptyline, imipramine, cyproheptadine,etc.), H₁ receptor antagonists/inverse agonists (e.g., buclizine,mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty acids,amitriptyline, chlorpheniramine maleate, etc.), D₁/D₂ receptorantagonists (e.g., haloperidol, chlorpromazine, olanzapine, risperidone,quetiapine, etc.), Marinol, Megace, Megace ES, α₁-adrenergic receptorantagonists (such as doxazosin, carvedilol, propanolol, colonidine),Serefam, α₂-adrenergic receptor agonists (e.g., clonidine, guanfacine,etc.), some beta blockers such as propanolol, natural or synthetic CB₁receptor agonists (e.g., THC or dronabinol (found in Cannabis),tetrahydrocannibinol, diphenydramine, promethazine, B vitaminsupplements, nabilone, JWH-018 etc.), Corticosteroids (e.g. prednisoneor dexamethasone), Sodium valproate (Depakote), Megestrol, Pregabalin,Sulfonylurea antidiabetic drugs such as glibenclamide andchlorpropamide, steroids (including, without limitation, boldenone,oxymetholone, dexamethasone, or methandrostenolone, prednisone,hydrocortisone, oxandrolone, nandrolone, testosterone), some kappaopioid receptor agonists such as tifluadom, hormones such asmederoxyprogesteronemirtazapine (Remeron), a tetracyclic antidepressant;cyproheptadine (Periactin), an antihistamine; nandrolone, oxymetholone,and oxandrolone (Anadrol-50, Durabolin, Hybolin, anti-IL6 antibody,selective androgen receptor modulator (“SARM”), Oxandrin, and otherbrand names), VT-122 (a coadministration of propranolol and etodolac),type 4 melanocortin receptor antagonis, IL6 antagonist, syntheticghrelin, myostatin decoy receptor, fast skeletal muscletroponin-activating substance, anticatabolic/anabolic transforming agentMT-102, celecoxib, testosterone, vitamin D, OHR/AVR118, soluble versionof the ActRIIB receptor, 5-HT₃ antagonists, Cox-2 inhibitor,thalidomide, omega-3 fatty acids, anticyclooxygenase-2 drugs andmegestrol acetate (Megace). In addition to these prescription drugs,fish oil (eicosapentaenoic acid or EPA), EATMOR, other vitamins andnatural or artificial appetite stimulants.

The method of claim 149, wherein the orexigenic drug is cyproheptadinehydrochloride.

The method according to any one of claim 127 or 149-151, wherein thesymptoms associated with appetite reduction is reduced by at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, or at least 95%.

The method according to any one of claim 127 or 149-151, wherein thesymptoms associated with appetite reduction is reduced by about 10% toabout 100%, about 20% to about 100%, about 30% to about 100%, about 40%to about 100%, about 50% to about 100%, about 60% to about 100%, about70% to about 100%, about 80% to about 100%, about 10% to about 90%,about 20% to about 90%, about 30% to about 90%, about 40% to about 90%,about 50% to about 90%, about 60% to about 90%, about 70% to about 90%,about 10% to about 80%, about 20% to about 80%, about 30% to about 80%,about 40% to about 80%, about 50% to about 80%, or about 60% to about80%, about 10% to about 70%, about 20% to about 70%, about 30% to about70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 127 or 149-151, wherein thesymptoms associated with reduction in the severity of appetite reductionis reduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95%.

The method according to any one of claim 127 or 149-151, wherein theseverity associated with reduction in appetite is reduced by about 10%to about 100%, about 20% to about 100%, about 30% to about 100%, about40% to about 100%, about 50% to about 100%, about 60% to about 100%,about 70% to about 100%, about 80% to about 100%, about 10% to about90%, about 20% to about 90%, about 30% to about 90%, about 40% to about90%, about 50% to about 90%, about 60% to about 90%, about 70% to about90%, about 10% to about 80%, about 20% to about 80%, about 30% to about80%, about 40% to about 80%, about 50% to about 80%, or about 60% toabout 80%, about 10% to about 70%, about 20% to about 70%, about 30% toabout 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 127 or 149-151, wherein thetreatment for appetite reduction results in an increase in weight by atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95%.

The method according to any one of claim 127 or 149-151, wherein thetreatment for appetite reduction results in an increase in weight byabout 10% to about 100%, about 20% to about 100%, about 30% to about100%, about 40% to about 100%, about 50% to about 100%, about 60% toabout 100%, about 70% to about 100%, about 80% to about 100%, about 10%to about 90%, about 20% to about 90%, about 30% to about 90%, about 40%to about 90%, about 50% to about 90%, about 60% to about 90%, about 70%to about 90%, about 10% to about 80%, about 20% to about 80%, about 30%to about 80%, about 40% to about 80%, about 50% to about 80%, or about60% to about 80%, about 10% to about 70%, about 20% to about 70%, about30% to about 70%, about 40% to about 70%, or about 50% to about 70%.

The method according to any one of claim 127 or 149-151, wherein thetreatment for appetite reduction results in an increase in height by atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95%.

The method according to any one of claim 127 or 149-151, wherein thetreatment for appetite reduction results in an increase in weight by atleast 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, atleast 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, atleast 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds,at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, atleast 25 pounds, at least 30 pounds, at least 50 pounds. In anotherembodiment, a therapeutic compound disclosed herein for the treatment ofappetite reduction results in an increase in weight by, e.g., from 0.5pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 pounds, from0.5 pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0.5 poundsto 5 pounds, from 1 pound to 15 pounds, from 1 pound to 10 pounds, from1 pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 pounds to tenpounds, from 2 pounds to 7.5 pounds.

The method according to any of claim 127 or 149-151, wherein thetreatment for appetite reduction increases the attentiveness of apatient by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90% or at least 95%.

The method according to any of claim 127 or 149-151, wherein thetreatment for appetite reduction increases the attentiveness of apatient by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

The method according to any one of claim 127 or 149-161, wherein thedose of the therapeutic compound to treat the reduction in appetite isin the range of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, atleast 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, atleast 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, atleast 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, atleast 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.

The method according to any one of claim 127 or 149-161, wherein thedose of the therapeutic compound to treat reduction in appetite is inthe range of about 0. 001 mg/kg/day to about 100 mg/kg/day.

The method according to any one of claim 127 or 149-161, wherein thedose of the therapeutic compound to treat the reduction in appetite isin the range of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to about 20mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to about 35mg/kg/day, about 0.001 mg/kg/day to about 40 mg/kg/day, about 0.001mg/kg/day to about 45 mg/kg/day, about 0.001 mg/kg/day to about 50mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001mg/kg/day to about 100 mg/kg/day.

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound to treat the reduction in appetite is administeredto an individual topical, sublingual, rectal, vaginal, trancutaneous,oral, inhaled, intranasal, subcutaneous, intravenous, enteral orparenteral.

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound to treat the reduction in appetite is administeredas a liquid, a solid, a semi-solid or an aerosol.

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound is formulated as a tablet, lozenge, orallydissolved strip, capsule, syrup, oral suspension, emulsion, granule,sprinkle or pellet.

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound is a long acting, sustained release, extendedrelease, immediate release, slow release, or controlled releasetherapeutic compound.

The method according to any of claim 1 or 23-35, wherein the therapeuticcompound is released over a period of about 3 days after administration,about 7 days after administration, about 10 days after administration,about 15 days after administration, about 20 days after administration,about 25 days after administration, about 30 days after administration,about 45 days after administration, about 60 days after administration,about 75 days after administration, or about 90 days afteradministration.

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound is released over a period of at least 3 days afteradministration, at least 7 days after administration, at least 10 daysafter administration, at least 15 days after administration, at least 20days after administration, at least 25 days after administration, atleast 30 days after administration, at least 45 days afteradministration, at least 60 days after administration, at least 75 daysafter administration, or at least 90 days after administration

The method according to any of claim 127 or 149-161, wherein thetherapeutic compound is released over a period of about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, about 6 days after administration or about 7 days ormore after administration.

The method according to any of claim 127 or 149-161, wherein thepharmaceutical composition includes pharmaceutical acceptablecomponents.

The method of claim 172, wherein the pharmaceutical acceptablecomponents is selected from the group consisting of a salt, asurfactant, an amino acid, a stabilizer or a buffer.

The method of claim 173, wherein the salt is selected from the groupconsisting of citric acid, sodium chloride, potassium chloride, sodiumsulfate, potassium nitrate, sodium phosphate monobasic or sodiumphosphate dibasic.

The method of claim 172, wherein the surfactant is a polysorbate.

The method of claim 175, wherein the polysorbate is selected from thegroup consisting of Tween 20, Tween 80, F68, F88, sorbitain esters,lipids, fatty acids or fatty esters.

A pharmaceutical composition for the treatment of an individual with adisorder associated with a psychological and/or neurological disorder,which comprises a therapeutic compound consisting of an amphetamineand/or a methylphenidate and a therapeutic compound to treat a reductionin appetite, thereby treating the individual.

The pharmaceutical composition of claim 177, wherein, the psychologicaland/or neurological disorder is selected from the group of migraine,anti-serotonergic side effects, narcolepsy, excessive sleepinessassociated with shift work, obstructive sleep apnea as an adjunct tocontinuous positive airways pressure (“CPAP”), exogenous obesity,disruptive behaviour disorder including oppositional defiant disorder(“ODD”) and conduct disorder (“CD”), obesity, depression (including,without limitation, augmentation of antidepressants in treatingrefractory depression and cancer-related depression), neural insult,fatigue (including, without limitation, disease-related fatigue inpatients with HIV, advanced cancer, multiple sclerosis, myotonicdystrophy, depression, fibromyalgia and hepatitis C), lethargy, bingeeating disorder, schizophrenia, sleep cycle disorder, cocaine addiction,Parkinson's Disease, combat and non-combat related PTSD and/or tic.

A pharmaceutical composition of claim 177, wherein the therapeuticcompound administered for the treatment of a psychological orneurological disorder is an amphetamine or a methylphenidate.

A pharmaceutical composition of claim 179, wherein the amphetamine ormethylphenidate is selected from the group consisting of OROSmethylphenidate (Concerta), dextroamphetamine immediate/sustainedrelease (Adderall/Adderall XR), dexmethylphenidate (Focalin), FocalinXR, Metadate CD, Metadate ER, NWP09, Dexedrine, dextroamphetamine(Dexedrine), Dexedrine Spansules, Methylin ER (Ritalin SR),methylphenidate (Ritalin), and methylphenidate CR, Ritalin, Ritalin LA,SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Daytrana,Equasym, Dixirit, Kapvay, Daytrana Patch, Methylin chewable, Methylinliquid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTS patch,Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa,Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil,Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, Remeron,Cymbalta, Nardil, Parnate, Emsam patch, Haldol, Orap, Prolixin,Mellaril, Thorazine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa,Seroquel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan,Buspar, Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid,Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, Topamax,Neurontin and the therapeutic compounds identified in Table 1.

A pharmaceutical composition according to any one of claims 177-180,wherein the symptoms associated with attention deficit disorder isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 177-180,wherein the severity associated with attention deficit disorder isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 177-180,wherein the symptoms associated with attention deficit disorder isreduced by about about 10% to about 100%, about 20% to about 100%, about30% to about 100%, about 40% to about 100%, about 50% to about 100%,about 60% to about 100%, about 70% to about 100%, about 80% to about100%, about 10% to about 90%, about 20% to about 90%, about 30% to about90%, about 40% to about 90%, about 50% to about 90%, about 60% to about90%, about 70% to about 90%, about 10% to about 80%, about 20% to about80%, about 30% to about 80%, about 40% to about 80%, about 50% to about80%, or about 60% to about 80%, about 10% to about 70%, about 20% toabout 70%, about 30% to about 70%, about 40% to about 70%, or about 50%to about 70%.

A pharmaceutical composition according to any one of claims 177-180,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of at least 0.001 mg/kg/day, at least0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50mg/kg/day.

A pharmaceutical composition according to any one of claims 177-180,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of about 0. 001 mg/kg/day to about 100mg/kg/day.

A pharmaceutical composition according to any one of claims 177-180,wherein the dose of the therapeutic compound to treat the attentiondeficit disorder is in the range of about 0.001 mg/kg/day to about 10mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day.

A pharmaceutical composition according to any one of claims 177-180,wherein the therapeutic compound to treat the attention deficit disorderis administered to an individual topical, sublingual, rectal, vaginal,trancutaneous, oral, inhaled, intranasal, subcutaneous, intravenous,enteral or parenteral.

A pharmaceutical composition according to any one of claims 177-180,wherein the therapeutic compound to treat the attention deficit disorderis administered as a liquid, a solid, a semi-solid or an aerosol.

A pharmaceutical composition according to any one of claims 177-180,wherein the therapeutic compound is formulated as a tablet, lozenge,orally dissolved strip, capsule, syrup, oral suspension, emulsion,granule, sprinkle or pellet.

A pharmaceutical composition according to claim 177, wherein thetherapeutic compound is a long acting, sustained release, extendedrelease, immediate release, slow release, or controlled releasetherapeutic compound.

A pharmaceutical composition according to claim 190, wherein thetherapeutic compound is released over a period of about 3 days afteradministration, about 7 days after administration, about 10 days afteradministration, about 15 days after administration, about 20 days afteradministration, about 25 days after administration, about 30 days afteradministration, about 45 days after administration, about 60 days afteradministration, about 75 days after administration, or about 90 daysafter administration.

A pharmaceutical composition according to claim 190, wherein thetherapeutic compound is released over a period of at least 3 days afteradministration, at least 7 days after administration, at least 10 daysafter administration, at least 15 days after administration, at least 20days after administration, at least 25 days after administration, atleast 30 days after administration, at least 45 days afteradministration, at least 60 days after administration, at least 75 daysafter administration, or at least 90 days after administration

A pharmaceutical composition according to claim 190, wherein thetherapeutic compound is released over a period of about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, about 6 days after administration or about 7 days ormore after administration.

A pharmaceutical composition according to claim 177, wherein thepharmaceutical composition includes pharmaceutical acceptablecomponents.

A pharmaceutical composition according to claim 194, wherein thepharmaceutical acceptable components is selected from the groupconsisting of a salt, a surfactant, an amino acid, a stabilizer or abuffer.

A pharmaceutical composition according to claim 195, wherein the salt isselected from the group consisting of citric acid, sodium chloride,potassium chloride, sodium sulfate, potassium nitrate, sodium phosphatemonobasic or sodium phosphate dibasic.

A pharmaceutical composition according to 194, wherein the surfactant isa polysorbate.

A pharmaceutical composition according to claim 197, wherein thepolysorbate is selected from the group consisting of Tween 20, Tween 80,F68, F88, sorbitain esters, lipids, fatty acids or fatty esters.

A pharmaceutical composition according to claim 177, wherein thetherapeutic compound to treat a appetite reduction is an orexigenicdrug.

A pharmaceutical composition according to claim 199, wherein theorexigenic drug is selected from the group of: alcohol, GHB, and othersedatives such as some benzodiazepine and nonbenzodiazepinetranquilizers and sleeping pills, anti-depressants (some SSRIs,Mianserin, etc.), 5-HT_(2C) receptor antagonists/inverse agonists (e.g.,mirtazapine, mianserin, olanzapine, quetiapine, risperidone,amitriptyline, imipramine, cyproheptadine, etc.), H₁ receptorantagonists/inverse agonists (e.g., buclizine, mirtazapine, mianserin,olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlorpheniraminemaleate, etc.), D₁/D₂ receptor antagonists (e.g., haloperidol,chlorpromazine, olanzapine, risperidone, quetiapine, etc.), Marinol,Megace, Megace ES, α₁-adrenergic receptor antagonists (such asdoxazosin, carvedilol, propanolol, colonidine), Serefam, α₂-adrenergicreceptor agonists (e.g., clonidine, guanfacine, etc.), some betablockers such as propanolol, natural or synthetic CB₁ receptor agonists(e.g., THC or dronabinol (found in Cannabis), tetrahydrocannibinol,diphenydramine, promethazine, B vitamin supplements, nabilone, JWH-018etc.), Corticosteroids (e.g. prednisone or dexamethasone), Sodiumvalproate (Depakote), Megestrol, Pregabalin, Sulfonylurea antidiabeticdrugs such as glibenclamide and chlorpropamide, steroids (including,without limitation, boldenone, oxymetholone, dexamethasone, ormethandrostenolone, prednisone, hydrocortisone, oxandrolone, nandrolone,testosterone), some kappa opioid receptor agonists such as tifluadom,hormones such as mederoxyprogesteronemirtazapine (Remeron), atetracyclic antidepressant; cyproheptadine (Periactin), anantihistamine; nandrolone, oxymetholone, and oxandrolone (Anadrol-50,Durabolin, Hybolin, anti-IL6 antibody, selective androgen receptormodulator (“SARM”), Oxandrin, and other brand names), VT-122 (acoadministration of propranolol and etodolac), type 4 melanocortinreceptor antagonis, IL6 antagonist, synthetic ghrelin, myostatin decoyreceptor, fast skeletal muscle troponin-activating substance,anticatabolic/anabolic transforming agent MT-102, celecoxib,testosterone, vitamin D, OHR/AVR118, soluble version of the ActRIIBreceptor, 5-HT₃ antagonists, Cox-2 inhibitor, thalidomide, omega-3 fattyacids, anticyclooxygenase-2 drugs and megestrol acetate (Megace). Inaddition to these prescription drugs, fish oil (eicosapentaenoic acid orEPA), EATMOR, other vitamins and natural or artificial appetitestimulants.

A pharmaceutical composition according to claim 199, wherein theorexigenic drug is cyproheptadine hydrochloride.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the symptoms associated with appetite reduction isreduced by at least 10%, at least 15%, at least 20%, at least 25%, atleast 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the symptoms associated with appetite reduction isreduced by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the symptoms associated with reduction in the severityof appetite reduction is reduced by at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90% or at least95%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the severity associated with reduction in appetite isreduced by about 10% to about 100%, about 20% to about 100%, about 30%to about 100%, about 40% to about 100%, about 50% to about 100%, about60% to about 100%, about 70% to about 100%, about 80% to about 100%,about 10% to about 90%, about 20% to about 90%, about 30% to about 90%,about 40% to about 90%, about 50% to about 90%, about 60% to about 90%,about 70% to about 90%, about 10% to about 80%, about 20% to about 80%,about 30% to about 80%, about 40% to about 80%, about 50% to about 80%,or about 60% to about 80%, about 10% to about 70%, about 20% to about70%, about 30% to about 70%, about 40% to about 70%, or about 50% toabout 70%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction results in anincrease in weight by at least 10%, at least 15%, at least 20%, at least25%, at least 30%, at least 35%, at least 40%, at least 45%, at least50%, at least 55%, at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction results in anincrease in weight by about 10% to about 100%, about 20% to about 100%,about 30% to about 100%, about 40% to about 100%, about 50% to about100%, about 60% to about 100%, about 70% to about 100%, about 80% toabout 100%, about 10% to about 90%, about 20% to about 90%, about 30% toabout 90%, about 40% to about 90%, about 50% to about 90%, about 60% toabout 90%, about 70% to about 90%, about 10% to about 80%, about 20% toabout 80%, about 30% to about 80%, about 40% to about 80%, about 50% toabout 80%, or about 60% to about 80%, about 10% to about 70%, about 20%to about 70%, about 30% to about 70%, about 40% to about 70%, or about50% to about 70%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction results in anincrease in height by at least 10%, at least 15%, at least 20%, at least25%, at least 30%, at least 35%, at least 40%, at least 45%, at least50%, at least 55%, at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction results in anincrease in weight by at least 0.5 pounds, at least 1 pound, at least1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least 3 pounds,at least 3.5 pounds, at least 4 pounds, at least 4.5 pounds, at least 5pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, atleast 7 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5pounds, at least 9 pounds, at least 9.5 pounds, at least 10 pounds, atleast 10.5 pounds, at least 11 pounds, at least 11.5 pounds, at least 12pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 pounds,at least 14 pounds, at least 14.5 pounds, at least 15 pounds, at least20 pounds, at least 25 pounds, at least 30 pounds, at least 50 pounds.In another embodiment, a therapeutic compound disclosed herein for thetreatment of appetite reduction results in an increase in weight by,e.g., from 0.5 pounds to 50 pounds, from 0.5 pounds to 30 pounds, from0.5 pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 poundsto 15 pounds, from 0.5 pounds to ten pounds, from 0.5 pounds to 7.5pounds, from 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 pound to 5pounds, from 2 pounds to ten pounds, from 2 pounds to 7.5 pounds.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction increases theattentiveness of a patient by at least 10%, at least 15%, at least 20%,at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, atleast 50%, at least 55%, at least 60%, at least 65%, at least 70%, atleast 75%, at least 80%, at least 85%, at least 90% or at least 95%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the treatment for appetite reduction increases theattentiveness of a patient by about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the dose of the therapeutic compound to treat thereduction in appetite is in the range of at least 0.001 mg/kg/day, atleast 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, atleast 5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, atleast 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, atleast 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or atleast 50 mg/kg/day.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the dose of the therapeutic compound to treat reductionin appetite is in the range of about 0. 001 mg/kg/day to about 100mg/kg/day.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the dose of the therapeutic compound to treat thereduction in appetite is in the range of about 0.001 mg/kg/day to about10 mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about 0.001mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day.

A pharmaceutical composition according to any one of claims 177 and199-201, wherein the therapeutic compound to treat the reduction inappetite is administered to an individual topical, sublingual, rectal,vaginal, trancutaneous, oral, inhaled, intranasal, subcutaneous,intravenous, enteral or parenteral.

A pharmaceutical composition according to any one of claims 177 and199-215, wherein the therapeutic compound to treat the reduction inappetite is administered as a liquid, a solid, a semi-solid or anaerosol.

A pharmaceutical composition according to any one of claims 177 and199-215, wherein the therapeutic compound is formulated as a tablet,lozenge, orally dissolved strip, capsule, syrup, oral suspension,emulsion, granule, sprinkle or pellet.

A pharmaceutical composition according to any one of claims 177 and199-215, wherein the therapeutic compound is a long acting, sustainedrelease, extended release, immediate release, slow release, orcontrolled release therapeutic compound.

A pharmaceutical composition according to any one of claims 177 and199-215, wherein the therapeutic compound is released over a period ofabout 3 days after administration, about 7 days after administration,about 10 days after administration, about 15 days after administration,about 20 days after administration, about 25 days after administration,about 30 days after administration, about 45 days after administration,about 60 days after administration, about 75 days after administration,or about 90 days after administration.

A pharmaceutical composition according to any one of claims 177 and199-218, wherein the therapeutic compound is released over a period ofat least 3 days after administration, at least 7 days afteradministration, at least 10 days after administration, at least 15 daysafter administration, at least 20 days after administration, at least 25days after administration, at least 30 days after administration, atleast 45 days after administration, at least 60 days afteradministration, at least 75 days after administration, or at least 90days after administration

A pharmaceutical composition according to any one of claims 199-218,wherein the therapeutic compound is released over a period of about 1day after administration, about 2 days after administration, about 3days after administration, about 4 days after administration, about 5days after administration, about 6 days after administration or about 7days or more after administration.

A pharmaceutical composition according to any one of claims 199-218,wherein the pharmaceutical composition includes pharmaceuticalacceptable components.

A pharmaceutical composition according to claim 222, wherein thepharmaceutical acceptable components is selected from the groupconsisting of a salt, a surfactant, an amino acid, a stabilizer or abuffer.

A pharmaceutical composition according to claim 223, wherein the salt isselected from the group consisting of citric acid, sodium chloride,potassium chloride, sodium sulfate, potassium nitrate, sodium phosphatemonobasic or sodium phosphate dibasic.

A pharmaceutical composition according to claim 222, wherein thesurfactant is a polysorbate.

A pharmaceutical composition according to claim 225, wherein thepolysorbate is selected from the group consisting of Tween 20, Tween 80,F68, F88, sorbitain esters, lipids, fatty acids or fatty esters.

A kit comprising a pharmaceutical composition of any preceding claim.

Certain embodiments of the present invention are described herein,including the best mode known to the inventors for carrying out theinvention. Of course, variations on these described embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventor expects skilled artisans to employsuch variations as appropriate, and the inventors intend for the presentinvention to be practiced otherwise than specifically described herein.Accordingly, this invention includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedembodiments in all possible variations thereof is encompassed by theinvention unless otherwise indicated herein or otherwise clearlycontradicted by context.

Groupings of alternative embodiments, elements, or steps of the presentinvention are not to be construed as limitations. Each group member maybe referred to and claimed individually or in any combination with othergroup members disclosed herein. It is anticipated that one or moremembers of a group may be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is deemed to contain the group asmodified thus fulfilling the written description of all Markush groupsused in the appended claims.

Unless otherwise indicated, all numbers expressing a characteristic,item, quantity, parameter, property, term, and so forth used in thepresent specification and claims are to be understood as being modifiedin all instances by the term “about.” As used herein, the term “about”means that the characteristic, item, quantity, parameter, property, orterm so qualified encompasses a range of plus or minus ten percent aboveand below the value of the stated characteristic, item, quantity,parameter, property, or term. Accordingly, unless indicated to thecontrary, the numerical parameters set forth in the specification andattached claims are approximations that may vary. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical indication shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and values setting forth the broad scope ofthe invention are approximations, the numerical ranges and values setforth in the specific examples are reported as precisely as possible.Any numerical range or value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Recitation of numerical ranges ofvalues herein is merely intended to serve as a shorthand method ofreferring individually to each separate numerical value falling withinthe range. Unless otherwise indicated herein, each individual value of anumerical range is incorporated into the present specification as if itwere individually recited herein.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the present invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein is intended merely to betterilluminate the present invention and does not pose a limitation on thescope of the invention otherwise claimed. No language in the presentspecification should be construed as indicating any non-claimed elementessential to the practice of the invention.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the present invention so claimed areinherently or expressly described and enabled herein.

All patents, patent publications, and other publications referenced andidentified in the present specification are individually and expresslyincorporated herein by reference in their entirety for the purpose ofdescribing and disclosing, for example, the compositions andmethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents isbased on the information available to the applicants and does notconstitute any admission as to the correctness of the dates or contentsof these documents.

What is claimed is:
 1. A method of reducing a loss of attentiveness inan individual suffering from an attention deficit disorder, wherein themethod reduces the CGI-I by a reduction in the score by 1 or more andfurther, wherein the individual's CGI-S score is reduced by at least 15%and attentiveness is increased by at least 10% as compared to a patienttaking only methylphenidate by administering to the patient in themorning a pharmaceutical composition comprising methylphenidate andcyproheptadine and wherein the pharmaceutical composition maintains meanpeak plasma for at least 6 hours.
 2. The method of reducing a loss ofattentiveness of claim 1, wherein the CGI-S score is reduced by at least20%.
 3. The method of reducing a loss of attentiveness of claim 1,wherein the CGI-S score is reduced by at least 25%.
 4. The method ofreducing a loss of attentiveness of claim 1, wherein the CGI-S score isreduced by at least 40%.
 5. The method of reducing a loss ofattentiveness of claim 1, wherein the CGI-S score is reduced by about10% to about 80%.
 6. The method of reducing a loss of attentiveness ofclaim 1, wherein the CGI-S score is reduced by about 10% to about 90%.7. The method of reducing a loss of attentiveness of claim 1, whereinthe CGI-S score is reduced by about 20% to about 70%.
 8. The method ofreducing a loss of attentiveness of claim 1, wherein the individualshows improvement in at least one of the following measures ofattentiveness, the p academic performance rating scale, ADD evaluationscale-3rd edition (ADDES-3),ADHD rating scale-IV (ADHD-RS-IV), youthself report (broadband instrument), Conners parent rating scale-revised(CPRS-R), Conners teacher rating scale-revised (CTRS-R), Conners 3self-reporting scale (Conner 3-SR; ages 8-18 y), home situa-tionsquestionnaire-revised, inattention/overactivity with aggression (IOWA)Conners teacher's rating scale, Swanson Nolan and Pelham IV scale(SNAP-IV), Swanson Kotkin Agler M-Flynn and Pelham (SKAMP), VanderbiltADHD diagnostic parent rating scale (VADPRS), Vanderbilt ADHD diagnosticteacher rating scale (VADTRS), behavior assess-ment system forchildren-2nd edition (BASC-2) or the Con-ners rating scale long version.9. The method of reducing a loss of attentiveness of claim 1, whereinthe CGI-S score is reduced by 1 or more as compared to a patientreceiving methylphenidate alone.
 10. The method of reducing a loss ofattentiveness of claim 1, wherein the mean peak plasma level ismaintained through lunch following administration in the morning.